PubMed Health⌕ Search

Biomedical subjects

I Fuse

Publications and source records attributed to I Fuse.

At least 55 records · Page 3Linked to original sources
PubMed1993

Paroxysmal nocturnal hemoglobinuria with myelofibrosis: progression to acute myeloblastic leukemia.

A 58-year-old male was diagnosed as having paroxysmal nocturnal hemoglobinuria (PNH) with myelofibrosis in 1984. The administration of hydroxyurea and low dose splenic irradiation were initiated for abdominal distention due to splenomegaly in 1987. In May 1990 the patient developed smouldering acute myeloblastic leukemia (AML); and the blasts proliferated in response to G-CSF administered for refractory pneumonia. The patient died of pneumonia and pleural involvement of leukemia in September 1990. FACS analysis of the blasts using anti-decay accelerating factor (DAF) (CD55) and CD59 (membrane attack complex inhibition factor: MACIF) monoclonal antibodies demonstrated that 25.5% and/or 87.3% of the blasts were negative for DAF or CD59 respectively. There is the earlier evidence that about 90% leukemic myeloblasts from non-PNH AML patients are positive for DAF, and nearly 100% of non-PNH neutrophils have been shown to be positive for both DAF and CD59. Our data suggest that the leukemic blasts from this patient may have derived from the PNH clone.

Antigens, CD↗
PubMed1993

[Platelets-morphology, shape changing factor, and platelet agglutinating factor. TTP Research Group].

The morphology of circulating platelets in thrombotic thrombocytopenic purpura (TTP) was studied, and basic mechanism of the characteristic shape abnormality found in TTP was investigated in in vitro condition. The platelet shape was spineless sphere (spherical platelets without pseudopods), and shape change persisted 2 months after remission. This type of platelets were produced by long term of activation of normal resting platelets by several agonists except ADP, and induced by dysfunction of both microtubules and microfilaments. These suggest that the shape change in TTP is not specific, but a good parameter for the activity of TTP. PAF activity by the method of Kelton et al. (1984) was detected in only 1 out of 30 samples from 10 patients. PSCF activity was found in 9 out of 29 samples from 10 patients independently from disease activity. Both activities does not reflect the activity of TTP.

Blood Coagulation Factors↗
PubMed1993

[Clinical manifestations and laboratory findings of thrombotic thrombocytopenic purpura].

Clinical manifestations and laboratory findings in 40 patients with thrombotic thrombocytopenic purpura (TTP) in Japan are reviewed. The most common clinical features were central neurological sings. jaundice, fever, hemorrhagic tendency, and renal abnormalities. Laboratory tests showed anemia, thrombocytopenia, hyperbilirubinemia, high serum LDH levels, and low serum haptoglobin levels. BUN and serum creatinine levels were elevated only in about 15% of the patients, although microscopic hematuria and proteinuria were observed more frequently (about 70%). Autoantibodies, such as antinuclear antibody and rheumatoid factor, were also observed in 4% to 9% of the patients. Coagulation and fibrinolysis studies showed normal values in the majority of the patients, suggesting intravascular generation of thrombin and plasmin was minimal in TTP.

Adolescent↗
PubMed1992

Immunoaffinity purification and cDNA cloning of human platelet prostaglandin endoperoxide synthase (cyclooxygenase).

The cDNA for prostaglandin endoperoxide synthase (cyclooxygenase) was cloned from human platelets by the polymerase chain reaction amplification method, and the primary structure of the enzyme was deduced from the nucleotide sequence. The enzyme was composed of 599 amino acids including 23-amino acid signal sequence, and the calculated molecular weight of the mature protein was 65,995. The enzyme was immunoaffinity-purified from human platelets. The N-terminal amino acid sequence determined by Edman degradation was Ala-Asp-Pro-Gly-Ala-Pro-Thr-Pro-, and the result confirmed the primary structure of the enzyme, which was deduced from the cDNA sequence.

Acetylation↗
PubMed1992

[Analysis of platelet shape change, inositol metabolism, and Ca mobilization in patients with platelet dysfunction].

Agonists-induced platelet shape change, inositol metabolism, and Ca mobilization were investigated in patients with various platelet dysfunctions. The platelet shape change determined by our method revealed that arachidonate-induced platelet shape change was completely defective in patients with cyclo-oxygenase (CO) deficiency (A). STA2-induced platelet shape change was also defective in one of five patients with impaired aggregation to STA2 (B). Thrombin-induced platelet shape change was weak in patients with Bernard-Soulier syndrome. In patient with Hermansky-Pudlak syndrome, the platelets did not respond normally to STA2, arachidonate or PMA. These findings suggested that the determinations of platelet shape change by our method was useful in diagnosing platelet dysfunctions. Inositol metabolism and Ca mobilization in response to thrombin, STA2, or NaF were also investigated in patient A,B, and impaired aggregation to A23187 in patient C. The responses were normal in patient A, suggested that CO activity did not affect them. Inositol metabolism was also normal in patient C, although Ca mobilization in response to A23187 was delayed, and that in response to thrombin was defective in the absence of extracellular Ca2+. This suggests that the patient's platelets have a defective IP3-induced Ca mobilization pathway. STA2 selectively failed to induce IP3 formation and Ca mobilization in patient B, although 3H-labelled thromboxane ligand (3H-U46619) bound to the patient's platelets, normally. These findings suggested that the patient's platelets have a defect in postreceptor signal transduction, especially thromboxane receptor-mediated phospholipase C activation pathway.

Blood Platelet Disorders↗
PubMed1992

[PI metabolism and Ca mobilization in patients with platelet dysfunction].

The effect of STA2, thrombin and NaF on PI metabolism and Ca mobilization was investigated in patients with three kinds of platelet dysfunction, one each with platelet cyclo-oxygenase deficiency (A), defective aggregation to A23187 (B) and defective aggregation to STA2 (C). These responses were normal in patient (A), suggesting cyclooxygenase activity did not affect PI metabolism and Ca mobilization. PI metabolism was also normal in (B), although Ca mobilization in response to A23187 was delayed and that in response to thrombin was defective in the presence of extracellular Ca2+. This suggests that the patient's platelets have a defective IP3-induced Ca mobilization pathway. STA2 selectively failed to induce IP3 formation and Ca mobilization in (C), although 3H-labelled thromboxane ligand (3H-U46619) bound to the patient's platelets normally. It was suggested that the patient's platelets have a defect in postreceptor signal transduction, especially thromboxane receptor-mediated PLC activation pathway.

Blood Coagulation Disorders↗
PubMed1992

[Hemostatic control in platelet dysfunction and abnormality by DDAVP].

DDAVP infusion shortens the bleeding time in patients with some types of platelet dysfunction and may be useful for hemostatic control. In order to clarify the mechanism of DDAVP to correct or bypass the release defect, we examined the effect in 17 patients with prolonged bleeding time, i.e., 11 with various kinds of platelet dysfunction, 4 with idiopathic thrombocytopenic purpura (ITP), 1 with chronic myelocytic leukemia (CML), and in an aspirin-ingested volunteer. DDAVP shortened the bleeding time in 9 patients with platelet dysfunctions, one with ITP, and the one aspirin ingested volunteer. No improvement was found in the aggregability and the retention rates, and no signs of activation occurred in the platelet shape. The RCof was elevated in all of the patients after the infusion. Our data suggests that DDAVP improves the hemostasis through primary aggregation and release of dense bodies, and not directly through an increase of RCof.

Bleeding Time↗
PubMed1991

Consumption coagulopathy associated with left atrial thrombosis.

Three patients with consumption coagulopathy due to left atrial thrombosis associated with mitral valve disease are described. They had hypofibrinogenemia (0.7-1.7 g/L), mild thrombocytopenia (104-117 x 10(9)/L), and elevated fibrinos/fibrin degradation products (FDP) (20-64 micrograms/ml). Two patients had bleeding symptoms, and one of these also had two episodes of transient ischemic attack. One without bleeding symptoms had three episodes of transient ischemic attack and repeated retinal vein thrombosis. In two patients, preoperative anticoagulation with either heparin or nafamostat mesilate was followed by an increase in plasma fibrinogen level from 0.7 to 5.6 g/L and a decrease in FDP from 64 to 8 micrograms/ml in one patient, and fibrinogen from 1.0 to 2.8 g/L and FDP from 40 to 5 micrograms/mL in another patient. The mitral valve replacement and thrombectomy were performed uneventfully, and their coagulopathy disappeared thereafter. These three patients had a lower platelet count and a shorter platelet survival time than another three patients with mitral valve disease of a similar severity but without coagulopathy. Hemostatic evaluation should be performed in patients suspected of intracardiac thrombosis.

Disseminated Intravascular Coagulation↗
PubMed1989

Phorbol ester, 1,2-diacylglycerol, and collagen induce inhibition of arachidonic acid incorporation into phospholipids in human platelets.

We have shown that phorbol myristate acetate (PMA) enhanced A-23187-induced arachidonate release and thromboxane synthesis in human platelets (Mobley, A., and Tai, H. H. (1985) Biochem. Biophys. Res. Commun. 130, 717-723). The mechanism of enhancement by PMA was not elucidated. In the present study, we have shown that PMA-treated platelets exhibited significantly less [1-14C]arachidonate incorporation than did control platelets. However, no significant change in uptake of labeled linoleate or oleate was observed by PMA treatment. Examination of the two enzyme activities involved in arachidonate incorporation into phospholipids indicated that both arachidonoyl-coenzyme A (CoA) synthase and arachidonoyl-CoA lysophosphatide acyltransferase were inactivated following treatment with PMA or 1-oleoyl-2-acetyl glycerol. When platelets were stimulated with A-23187 plus PMA which produced a significant synergism in thromboxane synthesis, both enzyme activities were substantially less than those in platelets treated with A-23187 alone. In addition to PMA and 1-oleoyl-2-acetyl glycerol induced decreases in both enzyme activities, collagen, a platelet agonist which can activate protein kinase C (Ca2+/phospholipid-dependent enzyme), was also found to cause a concentration-dependent attenuation of both enzyme activities. These results suggest that protein kinase C activation induced by PMA or collagen may cause inactivation of both arachidonoyl-CoA synthase and arachidonoyl-CoA lysophosphatide acyltransferase resulting in inhibition of the reincorporation of arachidonate released by A-23187 and, consequently, greater availability of arachidonate for thromboxane synthesis.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

Characterization of platelet cytoplasmic Ca2+ mobilization in patients with congenital cyclo-oxygenase deficiency and with defective platelet aggregation to A23187.

Agonist-induced platelet cytoplasmic Ca2+ concentrations ([Ca2+]i) in patients with congenital cyclo-oxygenase deficiency (A) and with impaired aggregation to A23187 (B) were measured with aequorin in the presence or absence of extracellular Ca2+. The influence of TMB-8 or ONO3708 on agonist-induced [Ca2+]i in those platelets was also investigated. In Patient 1, there was a single aequorin luminescence peak in response to arachidonate, which was a thromboxane A2(TXA2) independent Ca2+ influx. The luminescence peak due to the formation of TXA2 was not detectable. The A23187-induced [Ca2+] i was decreased in the presence of extracellular Ca2+, but was within normal limits in the absence of extracellular Ca2+. A thrombin or STA2-induced elevation of [Ca2+] i was always within normal limits under any conditions. These results suggest that cyclo-oxygenase activity (CO activity) contributes to the A23187-induced Ca2+ influx, but does not contribute to the Ca2+ release from intracellular stores, and that the thrombin or STA2-induced Ca2+ influx and release do not depend on the CO activity. In Patient 2, the time lag from the addition of A23187 to the aequorin luminescence peak was found both in the presence and absence of extracellular Ca2+, which was more obvious in the latter. This A23187-induced elevation of [Ca2+] i disappeared after treatment of the platelets with TMB-8 in the absence of extracellular Ca2+, which is rarely seen in normal platelets. The most striking finding was that the thrombin-induced rise in [Ca2+] i in the absence of extracellular Ca2+ was not detectable. These findings might be closely related to abnormal platelet function in this patient.

Blood Platelet Disorders↗
PubMed1988

Does protein kinase C activation mediate thrombin-induced arachidonate release in human platelets?

Thrombin stimulated rapid formation of diacylglycerol, inositol 1,4,5-trisphosphate (IP3) and thromboxane B2 (TXB2) in human platelets. Formation of diacylglycerol and IP3 appeared to precede that of TXB2. Activation of protein kinase C by diacylglycerol combining with Ca+2 mobilization by IP3 has been implicated in mediating arachidonate release. However, addition of the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) to platelet suspension did not inhibit thrombin-stimulated arachidonate release and TXB2 synthesis, whereas addition of the Ca+2 antagonist, 3,4,5-trimethoxybenzoic acid 8-(diethylamino) octyl ester (TMB-8) or the calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) abolished arachidonate release. The correlation of IP3 production with arachidonate release on increasing the concentrations of thrombin was further examined. IP3 production reached near maximum at 0.2 U/ml, whereas TXB2 synthesis continued to increase at 1 U/ml. These results suggest that protein kinase C activation may not mediate arachidonate release and that Ca+2 mobilization by IP3 may only partially account for arachidonate release in platelets stimulated with relatively high concentrations of thrombin.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1987

Stimulations of arachidonate release and inositol-1,4,5-triphosphate formation are mediated by distinct G-proteins in human platelets.

Addition of fluoroaluminate to human platelet suspension stimulated thromboxane synthesis and inositol-1,4,5-triphosphate formation in a time and dose dependent manner. Neomycin inhibited markedly fluoroaluminate induced inositol-1,4,5-triphosphate formation without significantly affecting thromboxane synthesis. Preincubation of platelets with PGE1, also inhibited significantly inositol-1,4,5-triphosphate formation with modest reduction of thromboxane synthesis. On the contrary, pretreatment of platelets with pertussis toxin inhibited fluoroaluminate stimulated thromboxane synthesis without affecting inositol-1,4,5-triphosphate formation. Similarly, preincubation of platelets with phorbol ester, PMA, inhibited markedly thromboxane synthesis with modest reduction of inositol-1,4,5-triphosphate formation. These results indicate that inositol-1,4,5-triphosphate formation and arachidonate release and thromboxane synthesis are controlled separately and are mediated by different G-proteins which are coupled to phospholipase C and phospholipase A2 respectively in platelets.

Aluminum↗
PubMed1986

A defect of platelet release reaction in a patient with SLE: impaired platelet aggregation induced by phorbol ester with a normal phosphorylation of 40K protein.

A 37-year-old female who suffered from SLE had a bleeding disorder. At the time of initial evaluation, the main disease demonstrated was a delta-storage pool deficiency. After this improved, a marked decrease of aggregation still remained, when induced by either ADP, epinephrine, collagen, A23187, thrombin, or PAF-acether. Although arachidonate-induced aggregation was slightly decreased, thromboxane B2 was produced normally in response to exogenous arachidonate. The patient's endoperoxides and/or thromboxane A2 aggregated aspirin-treated platelets, though her platelets were themselves unresponsive. Impaired aggregability induced by TPA (12-0-tetradecanoylphorbol-13-acetate) or OAG (1-oleoyl-2-acetyl-glycerol) was also found. However, the phosphorylation of P43 and P20 induced by several stimulators including CA++ ionophore was normal, using 32P-labelled platelets. It is suggested that TPA or OAG-induced platelet aggregation requires not only the phosphorylation of those proteins, but also another unknown mechanism after the phosphorylation, and that the platelet dysfunction of this patient was due to a defect of some mechanism involving Ca++ uptake or mobilization of cytoplasmic Ca++ from intracellular storage sites.

Adenosine Diphosphate↗
PubMed1985

Different effects of three kinds of somatostatin (15-28, 1-14, 1-28) on rabbit's platelet aggregation.

We studied the different effects of three kinds of somatostatin (somatostatin 1-14, somatostatin 15-28, somatostatin 1-28) on the aggregation of rabbit's platelets. It was clarified that somatostatin 15-28 had inhibitory effects on rabbit's platelet aggregation stronger than somatostatin 1-14 did, and that somatostatin 1-28 did not have any such effects. These anti-aggregatory effects of somatostatin were stronger when induced by collagen than induced by ADP.

Adenosine Diphosphate↗