ISSN:0957-5235    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Anticardiolipin antibodies (ACA) were determined in 72 heavily transfused haemophiliacs, 43 HIV-positive and 29 HIV-negative. The presence of ACA was detected in 10 patients, all of them infected by HIV: 8 in CDC II, 1 in CDC III and 1 in CDC IV. The comparison with alterations of other laboratory markers in HIV-infected patients did not show any statistically significant difference between ACA-negative and -positive patients. In summary, ACA were found only in HIV-infected haemophiliacs. In this subgroup of patients the presence of ACA was not associated with progression to AIDS.

ISSN:0957-5235    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The factor VIII (FVIII) binding regions of the monoclonal anti-FVIII inhibitory antibody C5 and a human FVIII inhibitor antibody have previously been reported to be contained within amino acid residues 351 – 365 of FVIII. Localization of the binding regions of these two antibodies was based on their reactivity with four synthetic FVIII peptides. Nineteen synthetic FVIII peptides spanning the entire acidic region of the FVIII heavy chain have now been evaluated for the ability to inhibit the binding of C5 to FVIII in an ELISA assay. The smallest peptide tested that inhibited C5 binding to FVIII consisted of residues 351 — 361. Those peptides that were able to inhibit C5 binding in the ELISA assay were also able to neutralize the FVIII inhibitory activity of C5 in plasma. The FVIII inhibitory activity of two human FVIII inhibitor antibodies was also partially neutralized by peptides from this region. Evaluation of the pattern of peptides reactive with the three antibodies indicates that the binding regions of these antibodies are in very close proximity to each other, but are not identical. Their respective binding regions are contained within residues 351–361 (C5), 354–362 (inhibitor 1), and 342–354 (inhibitor 2). These results suggest that this 20 amino acid segment of the acidic region of the heavy chain of FVIII may be functionally important in the expression of FVIII procoagulant activity.

ISSN:0957-5235    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The correlation between lupus anticoagulant (LA) potency and anticardiolipin antibody (ACA) ELISA was found to be poor (r= 0.40) in a group of 56 patients accumulated by a haematology department mainly for studies of LA. This correlation was similar whether LAs were assessed by kaolin clotting time or activated partial thromboplastin time increments.When the more procoagulant phospholipid phosphatidyl serine, used in a calcium-containing buffer, was substituted for cardiolipin in the ELISA, the correlation with LA was only slightly improved (r= 0.58). In fact, binding of antibody from patient plasmas to blank wells, although quantitatively reduced, was found to correlate equally well with LA activity. LAs ate not necessarily phospholipid-binding antibodies but may interfere more generally with other surface-dependent processes in the clotting mechanism.

ISSN:0957-5235    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Dose-ranging studies with a batch of factor IX concentrate have been performed in a canine non-stasis model of thrombogenicity. Doses between 50 and 200 IU/kg were infused over a 30 min period, and beagles were found to be more sensitive than greyhounds with regard to subsequent alterations in haemostatic parameters over a 150 min period. In beagles we detected significant increases in plasma fibrin(ogen) degradation products and reduction in fibrinogen concentrations in a dose-related manner after infusion of factor DC concentrate over the range 50–150 IU/kg. Plasma fibrinopeptide A was the most sensitive marker of activation of coagulation with significantly increased levels after factor IX at 50 IU/kg compared with control infusions of albumin. Recovery of infused factor IX was similar to values reported in man. In these experiments, measurement of urinary fibrinopeptide A did not prove to be a useful indicator of thrombogenicity. In conclusion, the beagle non-stasis model will provide a sensitive method to quantify the unwanted thrombogenic activities associated with the use of high doses of certain factor IX concentrates.

ISSN:0957-5235    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Initial-rate kinetic studies of the activation of plasminogen by epithelial activator were performed in the absence and in the presence of fibrinogen and CNBr-digested fibrinogen, under assay conditions similar to those described by Hoylaettset al.(J Biol Chem, 257, 2912, 1982). In the purified System, and in the absence of any stimulator, Lys-plasminogen is more readily activated than Glu-plasminogen, with catalytic rate constants of 0.01 s-1and 0.0034 s-1and Michaelis constants of 1.2 μM and 3.5 μM respectively. With Glu-plasminogen, double reciprocal plots deviated from linearity at low concentrations of plasminogen, in agreement with the findings reported for melanoma activator. In the presence of fibrinogen, activation rates for both Lys and Glu-plasminogen were increased. (K= 0.017 and 0.041 s-1andK= 1.4 and 41 μM, respectively). In the presence of CNBr-fragments of fibrinogen, the Michaelis constant is lowered for both forms of plasminogen, (km= 0.3 μM) thus indicating high affinity and efficient activation of plasminogen on fibrin dot. Comparison of the kinetic data with those reported for melanoma activator suggest that even though the values of the kinetic constants are different, epithelial activator has a similar mechanism of action for the activation of plasminogen as the melanoma enzyme.

ISSN:0957-5235    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Lipopolysaccharide (LPS) stimulation of human monocytes in heparinized whole bloodin vitroas expressed by induced activity of thromboplastin, has been studied. An essential role of arachidonic acid (20:4) release was found. 2,4‘-dibromoacetophenone, a phospholipase A2inhibitor, totally blocked the induced synthesis of thromboplastin activity. Furthermore, nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, had an effect on the LPS-induced thromboplastin synthesis which varied from no inhibition in individuals insensitive to LPS (’low responders‘), up to 80% inhibition in the person with the highest response (’high responder‘) to LPS. Platelets were found to be partially responsible for this difference. Thus, monocytes from high responders cross-combined with platelets from low responders wete much less prone to LPS stimulation than they were in the presence of high responder platelets. Intake of acetylsalicylic acid caused a 50% increment of LPS-induced thromboplastin synthesis, and this effect was mediated by platelets.

ISSN:0957-5235    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The anti-aggregating activity of L-arginine and its analogues has been investigated in washed human platelets. The ability of these compounds to inhibit platelet aggregation induced by thrombin or collagen was mimicked by a change in the external pH of the buffer from pH 8.0 to pH 7.4. Of the several analogues tested, only benzoyl-l-arginine ethylester (BAEE) inhibited thrombin- but not collagen-induced platelet aggregation. In platelet-rich plasma, BAEE also inhibited platelet aggregation without inhibiting fibrin clot formation. These results suggest that the marked sensitivity of washed human platelets to small changes in the external pH may lead to misinterpretation of the anti-aggregatory potency of protonated test drugs. For work with human washed platelets a physiological sait solution with more buffering capacity than Krebs - bicarbonate (such as Tyrode — HEPES) is recommended.

ISSN:0957-5235    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Aprotinin is a polypeptide from bovine lung which has been known since 1930, and which has previously been administered to humans as a relatively non-specific protease inhibitor in a number of disease states. In 1987, a remarkable use for this drug was realized, when by chance, it was discovered that by infusing large doses of aprotinin during cardiac surgery, it was possible to greatly reduce the bleeding which had hitherto been regarded as normal in such operations. The aim of this article is to briefly review the biochemistry and pharmacology of aprotinin, and to describe the background to its use in preventing postoperative bleeding. The use of aprotinin in reducing bleeding after cardiac surgery is then described in detail, and outlined for other types of major surgery. The possible modes of action of aprotinin in reducing bleeding are discussed, with particular reference to the bleeding which follows cardiac surgery. The profound effect of aprotinin, given in a novel dosage to reverse the postoperative haemostatic defect suggests that this drug may abolish the need for blood transfusions in most patients after major surgery. In addition, it is dear that aprotinin will provide a potent tool to probe some of the remaining mysteries of the haemostatic process.

ISSN:0957-5235    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Considerable progress has been made recently in understanding the mechanisms and significance of coagulation activation in human malignancy. Neoplastic cells may activate coagulation reactions directly, that is through contact with coagulation factors; or indirectly by formation of cytokines capable of activating certain host cells such as macrophages or endothelial cells. Data suggest that at least two autoregulatory pathways involving components of coagulation and fibrinolysis pathways exist. In one of these, tumour cell procoagulants lead to generation of thrombin in the tumour periphery. Thrombin is a mitogen that may also contribute to tumour stoma formation. Alternatively, tumour cells may express urokinase responsible for generation of cell surface-related proteolysis that may facilitate tumour cell proliferation, invasion and metastasis. An appreciation of these diverse mechanisms may permit rational design of clinical trials of agents capable of interrupting relevant pathways.

ISSN:0957-5235    

出版商:OVID    

年代:1990

数据来源: OVID