摘要:

KRDS (Lys-Arg-Asp-Ser), a tetrapeptide from human lactotransferrin, was tested for its effects in vitro on dog platelet function and in vivo on femoral arterial thrombus formation in dogs. KRDS inhibited ADP (8 μM)-induced platelet aggregation (IC50: 350 μM) and arachidonic acid (2 mM)-induced thromboxane B2 generation (IC50: 175 μM). In addition, the thrombin (0.2 U/ml)-induced serotonin release was inhibited by KRDS (IC50: 525 μM) and the expression of alpha-granule membrane protein (GMP-140) was also inhibited (IC50: 350 μM). The results show that KRDS is an inhibitor for platelet aggregation and secretion to which the inhibition is more potent. Meanwhile, in the experiment of arterial thrombosis in dogs, KRDS (5 μM/kg) and 125I-SZ-51 (a monoclonal antibody against GMP-140) were injected before operation and immediately after the thrombus formation, respectively. In the KRDS group, the weight of removed thrombi was reduced to 50% of that in controls and the radioactivity per mg of labeled thrombi to 33.3% while in blood the radioactivity increased 2 times that in controls at the 4th hour after the injection of 125I-SZ-51. The radioactivity ratio between removed thrombi and blood was only 16% of that in controls. These results indicate that KRDS can inhibit thrombus formation in vivo and is a promising antithrombotic

ISSN:1424-8832    

DOI:10.1159/000216284

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

An abnormal fibrinogen, denoted as ‘fibrinogen Milano IV, has been found in a 36-year-old woman without any bleeding manifestations or thrombotic tendency. Routine coagulation studies revealed prolonged thrombin and reptilase clotting times, very low plasma fibrinogen concentration determined by the functional assay but a normal fibrinogen concentration measured by the immunologic assay. Turbidity curves, measured following addition of thrombin to purified fibrinogen Milano IV, both in presence of calcium or EDTA, were markedly delayed. Release of fibrinopeptide B by thrombin was normal, whereas only half the normal amount of fibrinopeptide A was cleaved. The fibrinopeptide A peak of fibrinogen was preceded by an abnormal fibrinopeptide A*. Both peaks were collected for amino acid analysis which showed an exchange of arginine by histidine in position 16 of the Aα chain of the fibrinopeptide

ISSN:1424-8832    

DOI:10.1159/000216285

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Four hemodialysis patients (1 male and 3 females, aged 29-40 years) with unusual recurrent vascular access or dialyzer thrombosis were studied to find out whether a hypercoagulable state exists. Measurements of euglobulin clot lysis time (ELT), fibrinogen, antithrombin III (AT III), protein C (PC), protein S (PS), tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI) were done. Results indicated that all patients had prolonged ELT, low tPA, elevated PAI, normal AT III, and PS. Three patients had elevated fibrinogen level and two had low PC. Danazol 200 mg orally once a day effectively prevented any further thrombosis. In 4 weeks’ time, all the abnormal coagulation studies normalized in addition to elevation of AT III, PC and PS. Only 1 female patient had a prolonged menstrual period, which was reversed by lowering the daily dose of danazol to 100 mg. No other side effects were encountered. These data indicate that hypofibrinolysis may play a major role in vascular access or dialyzer thrombosis and that low-dose danazol may provide an effective prophylaxis and treatment. Larger controlled studies are needed to confirm these finding

ISSN:1424-8832    

DOI:10.1159/000216286

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

To estimate the degree of coagulopathy in abdominal sepsis, we measured the plasma levels of prothrombin fragment 1+2 (F1+2), thrombin-antithrombin III complex (TAT) and plasmin-α2-plasmin inhibitor complex (PIC) by the enzyme-linked immunosorbent assay in 38 patients with disseminated intravascular coagulation (DIC). In 20 patients with DIC due to abdominal sepsis, plasma levels of F1+2, TAT and PIC were 2.6 nmol/l, 27.9 μg/l and 1.5 μg/ml, respectively, with a mean antithrombin III (AT III) activity of 41.7%. F1+2, TAT, PIC and AT III levels were 4.7 nmol/l, 75.8 μg/l, 8.8 μg/ml and 70.9% in 18 patients with DIC as the result of malignancy. Though AT III levels in DIC due to sepsis were lower than those in DIC due to malignancy, the levels of F1+2, TAT and PIC in the former were not significantly more increased than those in the latter. The plasma levels of F1+2 were positively correlated with TAT and PIC in DIC patients with malignancy; however, there was no correlation between F1+2 and TAT or PIC in DIC patients with sepsis. In addition, the levels of serum albumin in the two groups were similar. These results suggest that activation of coagulation and fibrinolytic systems may not be so prominent in cases of DIC due to abdominal sepsis, compared to related events in DIC due to malignancy. It is also suggested that the depletion of AT III in cases of sepsis is not only caused by a consumption related to intravascular coagulation or to an alternate distribution of protein. It may relate to nonspecific proteolytic degradation by granulocytic proteinases. F1+2 may be more suitable than TAT for the evaluation of the coagulopathy in DIC patients with sepsis.

ISSN:1424-8832    

DOI:10.1159/000216287

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

39 human immunodeficiency-virus-1 (HIV-1 )-positive hemophiliacs who had been regularly treated with non-virus-inactivated intermediate-purity factor VIII concentrates were divided into two groups. Group A consisted of 21 patients with a CD4/CD8 cell ratio of less than 1.0 and group B of 18 patients with a CD4/CD8 cell ratio of greater than 1.0. All patients of group A were switched to a high-purity virus-inactivated factor VIII concentrate, whereas patients of group B continued to receive the intermediate-purity concentrate. There was no significant difference in the average decline of CD4 cells between the two groups during the observation period. 9 patients of group A and 4 patients of group B developed AIDS. 5 patients of group A but 11 patients of group B remained clinically asymptomatic. We conclude that the 15-fold increase in purity of the factor VIII concentrate had no apparent beneficial effect on the CD4 cell counts in this patient group.

ISSN:1424-8832    

DOI:10.1159/000216288

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Immunoglobulins isolated from egg yolk (IgYs) are a convenient source of polyclonal antibodies. Their purification is simple and the yields important (50 mg immunoglobulins/egg). Nevertheless their biochemical characteristics are different from those of rabbit antibodies generally used for the study of molecular defects of plasmatic and platelet proteins. Provided standardization is achieved, IgYs can be used for immunoelectrophoresis, immunoprecipitation or immunoblotting assays. We describe here the electrophoretic and immunoblotting conditions employed to explore human plasmatic and platelet von Willebrand factor (vWF) and human platelet GP Ilb-IHa using IgYs. These two proteins are involved in primary hemostasis and their absence or abnormality is responsible for hereditary bleeding disorders. The methods were applied to the characterization of patients with vWF or GP Ilb-IIIa defects and compared to classical mammalian IgG immunoelectrophoretic techniques. Results were further confirmed by flow cytometric analysis.

ISSN:1424-8832    

DOI:10.1159/000216289

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

M4, a fibrinolytic protease, was isolated from the venom of Crotalus molossus molossus. It has a pI of 9.6 and a molecular weight of 27,000. The protease hydrolyzes the Aα and Bβ chains of fibrinogen, and the α and β chains of fibrin. This activity was inhibited by EDTA and restored by Ca2+ or Zn2+, but not Mg2+. The protease hydrolyzed hide powder azure and casein, but it had no effect on collagen, hyaluronic acid, complement or synthetic substrates for thrombin, plasmin or kallikrein. Subcutaneous injections into mice with doses as high as 100 μg did not cause hemorrhage. This protease may have therapeutic use as a thrombolytic agent.

ISSN:1424-8832    

DOI:10.1159/000216290

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000216291

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000216292

出版商:S. Karger AG    

年代:1992

数据来源: Karger