摘要:

Platelets contain approximately 3% of the total circulating pool of fibrinogen (fg). Immunofluorescence and subcellular fractionation reveal that platelet fg is stored within intracellular structures which have been confirmed asα-granules by immunoelectronmicroscopy. The nature, origin(s) and possible function(s) ofα-granular fg have long been a point of controversy. Many early investigations into the properties of platelet fg were constrained by proteolysis, plasma fg contamination and lack of knowledge ofγ-chain heterogeneity. Later studies on the biochemistry and origins ofα-granular proteins resulted in the general consensus that platelet fg was not only identical to the major form within plasma but was almost certainly biosynthesised within the platelet precursor cell, the megakaryocyte (MK). However, the recent discovery of endocytic and pinocytic pathways within both MKs and platelets has requestioned the origin of manyα-granular proteins, including fg, resulting in reappraisal of early data, and a series of experiments which culminated in the study of fg mRNA expression in purified MKs and platelets. These studies suggest thatα-granular fg is derived from the plasma pool via a Gp IIb/IIIa mediated endocytic mechanism.

ISSN:0953-7104    

DOI:10.3109/09537109209013161

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0953-7104    

DOI:10.3109/09537109209013162

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Two double blind crossover studies have been carried out in healthy volunteers to determine the effect on platelet behaviour and on blood coagulation of treatment with atenolol and with a fixed combination of atenolol and nifedipine. The first study compared atenolol with placebo, whilst the second compared atenolol alone with the combination of atenolol and nifedipine. Treatment with atenolol alone had no effect on platelet behaviour. In contrast, treatment with the combination of the beta blocker and the calcium antagonist gave rise to a small but significant increase in platelet dense granule release ex vivo in response to a wide range of agonists. This was not associated with any change in serum levels of thromboxane B2 nor with any alteration in plasma concentrations of platelet factor 4 and beta-thromboglobulin. Neither treatment had any effects on coagulation parameters. The mechanism and clinical significance of the observed increase in the extent of the platelet release reaction during combined atenolol/nifedipine treatment remain speculative.

ISSN:0953-7104    

DOI:10.3109/09537109209013163

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

It is known that both platelet-activating factor (PAF) acetylhydrolase and phospholipase A2can inactivate PAF. An enzyme with the ability to convert labelled PAF into lyso-PAF was detected in the culture medium of mouse calvaria cultured in serum-free BG Jb medium containing 0.1% bovine serum albumin. The enzyme was unable to degrade labelled long chain diacylphosphatidylcholine, and was inert to addition of Ca2+(10 mM) or EDTA (10 mM). The enzyme was inhibited by diisopropylfluorophosphate in a dose-dependent manner. Moreover, the enzyme was found to be acid-labile, in a similar manner to PAF acetylhydrolase in mouse plasma. Based on these data, the enzyme was identified as PAF acetylhydrolase.It is known that PAF acetylhydrolase in rat plasma is different from that in rat kidney cortex in its sensitivity to proteases. PAF acetylhydrolase in mouse calvaria was insensitive to trypsin and pronase, like PAF acetylhydrolase in mouse plasma, while PAF acetylhydrolase in mouse kidney cortex was sensitive. PAF acetylhydrolase activity in the culture medium increased time-dependently for at least 48 h. Treatment of calvaria for 12 h with cycloheximide (1μg/ml), an inhibitor of protein synthesis, almost completely prevented the appearance of acetylhydrolase activity in the culture medium. Thus, the results suggest that mouse calvaria synthesize PAF acetylhydrolase and release it extracellularly under no stimuli, and that the properties of the acetylhydrolase in calvaria are similar to those of the enzyme found in plasma. Therefore, mouse calvaria may be one of the origins of PAF acetylhydrolase in plasma.

ISSN:0953-7104    

DOI:10.3109/09537109209013164

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

The effects of the beta-adrenoceptor blockers (BAB) alprenolol, atenolol, metipranolol, oxprenolol, practolol and propranolol on platelet aggregation stimulated by ADP, thrombin and collagen were investigated. The BAB were divided into three groups according to their liposolubility and antiaggregatory activity. The first group consists of the highly active drugs alprenolol and propranolol; metipranolol and oxprenolol are in the second group; the least active atenolol and practolol are in the third group. Collagen induced platelet aggregation was inhibited by BAB to the highest extent, followed by inhibition of thrombin stimulated aggregation. ADP-induced aggregation was inhibited to the lowest extent.Consistent with the rank order of their partition coefficients, BAB inhibited aggregation with the following order of potency: propranolol>alprenolol>metipranolol>oxprenolol>practolol>atenolol. A positive correlation was found between inhibition of thrombin and collagen stimulated platelet aggregation and the partition coefficients of the individual drugs. A significant time-dependent inhibition of platelet aggregation developed within 30 s of exposure of blood platelets to BAB.

ISSN:0953-7104    

DOI:10.3109/09537109209013165

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Human platelets are activated by IgG immune complexes and undergo platelet aggregation and the release of granular contents. Recently, the receptor for IgG on human platelets has been identified and characterised. In contrast, it is not known if rabbit platelets carry Fc receptors. In this report we describe investigations to detect the presence of an Fc receptor on rabbit platelets. The Fc receptor was investigated using functional assays (platelet aggregation and14C-serotonin release), a direct binding assay, and an affinity precipitation assay. All of these methods gave consistently positive results using human platelets and consistently negative results using rabbit platelets, indicating that rabbit platelets do not carry Fc receptors. This inconsistency in the interactions of immune complexes with rabbit and human platelets indicates that rabbits are not ideal models for studying a number of human diseases that could be caused by immune complexes, including heparin-induced thrombocytopenia and certain immunological disorders such as systemic lupus erythematosus.

ISSN:0953-7104    

DOI:10.3109/09537109209013166

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Platelet number, plasma beta-thromboglobulin (beta-TG), spontaneous platelet aggregation (SPA), serum thromboxane B2(TXB2), and 6-keto-PGF101were assessed in 9 males with proven atherosclerosis (survivors of myocardial infarction, (MI) in a stable condition) and compared with values for 9 young, healthy controls. Results were obtained before and after 3-day treatment with aspirin. In addition, SPA was assessed before and after a tourniquet test. MI survivors had higher beta-TG (p<0.01) and SPA values (p<0.05), and a lower platelet count (p<0.05) than controls. Aspirin significantly attentuated all these changes. These data suggest that platelet function is increased in survivors of MI. Tourniquet-induced ischaemia significantly (p<0.05) enhanced SPA in MI survivors but not in controls. Aspirin did not inhibit SPA following ischaemia in contrast to its effect under pre-ischaemic conditions or in controls. It seems that the proaggregatory threshold is decreased in MI survivors. The results challenge the assumption that an acute coronary event with underlying atherosclerosis is due to an interaction between atherosclerosis plaque and normal platelets.

ISSN:0953-7104    

DOI:10.3109/09537109209013167

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Recombinant human erythropoietin is a successful treatment for the anaemia of renal failure. Its use has however been associated with thromboembolic complications. Changes in platelet number and behaviour in vitro were studied in: (1) 23 haemodialysis patients, and 10 continuous ambulatory peritoneal dialysis patients (CAPD) treated with erythropoietin (EPO); (2) 14 untreated dialysis patients (7 haemodialysis, 7 CAPD), with intrinsically high haemoglobins; and (3) 23 age-matched non-uraemic normal controls.All patients treated with erythropoietin had a significant rise in haemoglobin (23 haemodialysis patients: pre-EPO median (range), 6.9 (5.1–8.1)g/dl; post-EPO, 10.9 (9.0‐–12.8)g/dl; 10 CAPD patients: pre-EPO, 7.8 (6.7–8.8)g/dl); post-EPO, 12.5 (9.9–14.3)g/dl; p<0.01). Platelet number was significantly reduced in CAPD patients (pre-EPO: 327 (210-745)&109/1; post-EPO: 240(198–359)&109/l; p<0.01) but not in haemodialysis patients.Spontaneous and collagen-induced whole blood platelet aggregation were significantly increased following erythropoietin treatment, both in haemodialysis (spontaneous platelet aggregation: pre-EPO, 39(12–78)%; post-EPO, 64(27–93)%, p<0.01, collagen-induced platelet aggregation: pre-EPO, 61(3–95)%; post-EPO, 74(21–93)% p<0.05), and CAPD patients (spontaneous platelet aggregation: pre-EPO, 38(18–81)%; post-EPO, 71 (41–95)%, p<0.01, collagen-induced platelet aggregation; pre-EPO, 73(28–95)%; post-EPO, 90(44–95)%, p<0.05). There was no significant change in aggregation to 1μM ADP.Spontaneous and collagen-induced platelet aggregation were significantly higher in erythropoietin treated patients and untreated CAPD controls with high haemoglobins compared to age and haemoglobin-matched non-uraemic normal individuals (23 normals: spontaneous platelet aggregation, 37(10–75)%; collagen-induced platelet aggregation, 43(6–94)%, p<0.001).Enhanced platelet aggregability is associated with vascular disorders. The increased red cell mass due to erythropoietin therapy may have physical and chemical effects on platelet function predisposing to thrombosis in this susceptible group of patients.

ISSN:0953-7104    

DOI:10.3109/09537109209013168

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Thrombosis and haemorrhage are major causes of morbidity in patients with myeloproliferative diseases. However, in chronic myeloid leukaemia (CML) these complications are less likely to occur. Therefore aggressive lowering of the platelet count has not been recommended in asymptomatic patients with CML. We describe 2 patients, 1 with acute myeloid leukaemia in remission and the other with CML in accelerated phase, in whom severe intracranial thrombotic complications unexpectedly developed: blindness in the former and brain stem damage with deep unconsciousness in the latter. During already ongoing cytostatic treatment both of them recovered dramatically, which seemed to have a temporal relationship to the reduction of their platelet counts. We consider that the thrombotic events in these patients were due to their high platelet counts and recommend treatment for symptomatic thrombocytosis.

ISSN:0953-7104    

DOI:10.3109/09537109209013169

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Aspirin, 250 mg/day, was administered to 14 normolipidemic healthy subjects for 7 days. Platelet lipid composition was determined in washed platelets by quantitating cholesterol to phospholipid molar ratio. Platelet membrane fluidity was measured by steady state fluorescence polarization using the probe diphenyl hexatriene. Upon 7 days aspirin ingestion platelet lipid composition was not altered. There was a sex-dependent effect of aspirin administration on platelet membrane fluidity. Whereas overall platelet membrane fluidity did not change at 37°C, there was a significant decrease in female subjects; the anisotropy parameter which is inversely related to membrane fluidity increased from 0.937±0.043–1.048±0.027 (p<0.01). In male subjects there was an increase in platelet membrane fluidity, which was significant at 25°C; the anisotropy parameter decreased from 1.350±0.039–1.283±0.023 (p<0.05). These results indicate that aspirin alters the membrane dynamics of platelets. This effect results from mechanisms other than alterations in platelet cholesterol or phospholipid content and operates in an opposite direction in men and women.

ISSN:0953-7104    

DOI:10.3109/09537109209013170

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor