ISSN:0953-7104    

DOI:10.3109/09537109309013223

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The most common hereditary disorders of platelet function are those in which there is decreased platelet aggregation in response to more than one of the commonly used aggregating agents, collagen, ADP, adrenaline and arachidonic acid. When measured, there is usually also a reduction in the extent of the platelet release reaction and often also thromboxane production. In a proportion of these cases it is possible to demonstrate that there is a decrease in or absence of the contents of the dense storage granules which accounts for the decrease in platelet responsiveness. In most other cases the primary cause of the decreased responsiveness has not been determined, although in some cases deficiency of cyclooxygenase or thromboxane synthetase has been demonstrated. Investigation of patients with these disorders is often difficult because the tests involved are difficult to subject to adequate quality control, their sensitivity and specificity has not been adequately defined, and lack of reproducibility renders it difficult in less severe cases to be certain of abnormality even after repeat tests. Much less common but of great interest are the disorders in which the primary abnormality is in one of the glycoproteins on the platelet surface. In Glanzmann's thrombasthenia glycoprotein IIb.IIIa is absent or greatly decreased leading to failure of activated platelets to bind fibrinogen to their surface. In contrast to the decrease in aggregation seen in the above disorders, the platelets do not aggregate at all in response to the usual aggregating agents. In Bernard-Soulier syndrome there are severe deficiencies of three glycoproteins, particularly lb, leading to inability to bind von Willebrand's factor and consequent inability of the platelets to aggregate in response to ristocetin. Study of the disorders of platelet function will continue to contribute to our ability to detect and treat these disorders and to our knowledge of platelet physiology and biochemistry.

ISSN:0953-7104    

DOI:10.3109/09537109309013224

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Ticlopidine and clopidogrel are two thienopyridines with potent and apparently irreversible platelet inhibitory properties. The antiplatelet effects are mainly directed against ADP-induced stimulation of platelet function, in particular ADP-induced inhibition of adenylyl cyclase stimulation. There is evidence for additional effects, including inhibition of agonist-induced intracellular Ca++mobilization, interference with GpIIb/IIIa receptor/agonist interaction and inhibition ofα-granule secretion. However, these actions are probably secondary to the ADP-antagonistic action.Thienopyridines do not directly interfere with arachidonic acid metabolism. The substances are inactive in vitro and have to undergo some form of bioactivation in vivo which requires 3 to 5 days of treatment for a maximum effect. The nature of the postulated active metabolite(s) is still unknown. From a pharmacological point of view, thienopyridines may be considered interesting alternatives to acetylsalicylic acid with particular value in shear-stress-mediated platelet activation, for example in prevention of acute thrombembolic risk in injury-related vessel stenosis.

ISSN:0953-7104    

DOI:10.3109/09537109309013225

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Blood platelets are produced in the circulation by fragmentation of long, slender processes of cytoplasm formed from the megakaryocyte, the parent cell of platelets. Fragmentation occurs at local constrictions, forming 6 to 15µm long, fusiform fragments (elongated proplatelets). The fusiforms transform into the circular, disc-shaped mature platelet by curving into a ring, which closes by fusion at the tips. The hole in the ring is finally filled in by a centripetal flow of membrane from the periphery. It is presumed that the curving of the fusiform is mediated by curving of its contained bundle of microtubules, which becomes the marginal bundle of the disc-shaped platelet. When curving begins in the fusiform, microtubules are closely associated with a membraneous tubule that becomes the submarginal tubule of the dense tubular system.

ISSN:0953-7104    

DOI:10.3109/09537109309013226

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Theramgene was isolated from a rat megakaryocyte cDNA library and encodes a GTP-binding protein with aMrof 25 000. In order to clarify the presence of theramprotein (ramp25) in human platelets, we tried to purifyramp25 from the sodium cholate extract of human platelet membranes by a combination of DEAE-Sephacel, Sephacryl S300HR, hydroxyapatite HCA-100S and DEAE-Toyopearl 650(S) column chromatographies. In the course of the purification, a specific antibody raised against a synthetic COOH-terminal peptide oframp25 was used. In conclusion,ramp25 was partially purified and was observed to be present in membrane fractions of human platelets.

ISSN:0953-7104    

DOI:10.3109/09537109309013227

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

We studied platelet aggregation and changes in cytosolic Ca++concentrations induced by cells isolated from 5 human tumor tissues (2 hepatocellular carcinomas, 1 colon carcinoma, 1 gastric carcinoma and 1 pancreatic carcinoma). A Platelet Ionized Calcium Aggregometer was used and washed, aequorin loaded platelets were employed. Tumor cells were able to induce aggregation and an increase in cytoplasmic Ca++concentrations in the presence of trace amounts (10µl) of PPP, while no aggregating response was found after addition of fibrinogen alone to washed platelets. The platelet aggregating activity of tumor cells was maintained in the presence of factor VII deficient plasma or of factor VIII deficient plasma, and disappeared completely when factor X deficient plasma was added to washed platelets. Furthermore, tumor cell induced platelet aggregation and Ca++movements were inhibited by hirudin (100 U/ml), a specific thrombin inhibitor, while concanavalin A (100µg/ml), a tissue factor inhibitor, had no effect. Finally, preincubation of neoplastic cells with HgCl2(0.5 mM), a cysteine protease inhibitor, markedly decreased their ability to induce aggregation and Ca++movements; on the contrary, incubation of cells with soybean trypsin inhibitor (10µg/ml), a serine protease inhibitor, or with concanavalin A (100µg/ml) had no effect. These data suggest that cells isolated from human tumor tissues activate platelet function through the generation of thrombin, due to a cysteine protease which directly activates factor X.

ISSN:0953-7104    

DOI:10.3109/09537109309013228

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Time-dependent changes in platelet aggregation in whole blood, platelet-rich plasma (PRP) and washed platelets were studied in streptozotocin-induced diabetic rats. Collagen-induced aggregation of whole blood and PRP from diabetic rats were significantly reduced within 8 weeks after induction of diabetes, although that in washed platelets were increased from 8 weeks. Plasma from diabetic rats within 8 weeks attenuated platelet aggregation, whereas diabetic plasma at 12 weeks showed no inhibitory effect. Insulin treatment normalized aggregation in whole blood and PRP and abolished the antiaggregatory activity of diabetic plasma. These results suggest the plasma antiaggregating activity appears in the early stage of diabetes, which may contribute to the hypoaggregation in whole blood and PRP. The inhibitory activity disappeared in the later stage. Plasma factor(s) accounting for the antiaggregatory effect of diabetic plasma has not yet characterized.

ISSN:0953-7104    

DOI:10.3109/09537109309013229

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

ISSN:0953-7104    

DOI:10.3109/09537109309013230

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Binding studies have shown that human platelets contain binding sites for insulin with a surface density similar to that described for other cells.1Evidence for a reduced number and affinity of human platelet membrane insulin binding sites in non-insulin dependent diabetes mellitus (NIDDM) has been provided.2However, the influence of insulin and insulin receptors on platelet function has not been completely investigated and clarified. Falcon et al3reported phosphorylation of a subunit of the insulin receptor on platelets in response to insulin, but no alterations were detected in cAMP formation or degradation, inositol phosphate formation or phosphorylation of proteins other than the receptor itself. On the other hand Trovati et al4found reduced platelet aggregation responses to ADP, PAF, epinephrine, collagen and arachidonate in the presence of 40µU/ml insulin. Their experience with an euglycemic-hyperinsulinemic clamp provided some further in vivo evidence to support the above mentioned findings. Platelet thromboxane A2formation was not altered in the presence of the hormone.

ISSN:0953-7104    

DOI:10.3109/09537109309013231

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor