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Biomedical subjects

M Colucci

Publications and source records attributed to M Colucci.

At least 73 records · Page 4Linked to original sources
PubMed1985

Thromboembolic complications and haemostatic changes in cyclosporin-treated cadaveric kidney allograft recipients.

The incidence of thromboembolic complications was compared retrospectively in 90 cadaveric kidney allograft recipients treated with cyclosporin and low-dose steroids and the same number of cadaveric kidney allograft recipients treated with azathioprine, antilymphocyte globulin, and high-dose steroids. In the cyclosporin group, 17 thromboembolic complications occurred in 13 patients: 10 pulmonary emboli, 1 renal vein thrombosis, 3 deep vein thromboses, and 3 haemorrhoidal thromboses. In the azathioprine group, the only thromboembolic complication was 1 episode of superficial thrombophlebitis. Haemostatic tests in cyclosporin-treated and azathioprine-treated patients and normal subjects (10 in each group) showed increased concentrations of factor VIII C, fibrinogen, antithrombin III, and protein C in the cyclosporin-treated patients. Adenosine-5'-diphosphate-induced platelet aggregation was also significantly enhanced in the cyclosporin group. The effect of cyclosporin on haemostasis may predispose to thromboembolic complications.

Azathioprine↗
PubMed1985

Failure to warfarin to affect the tissue factor activity and the metastatic potential of murine fibrosarcoma cells.

Vitamin K deficiency, either dietary or pharmacologically induced by warfarin, was unable to affect the metastatic capacity of cells from a benzopyrene-induced fibrosarcoma in C57BL/6J mice. The same cells had a procoagulant activity, of tissue thromboplastin type, which was also completely unaffected by vitamin K antagonism or deficiency. In another murine model of spontaneous metastasis we previously suggested that depression of a particular procoagulant such as a direct factor X activator might contribute to the antimetastatic activity of warfarin. The failure of vitamin K deficiency to affect both the procoagulant and the metastatic capacity of the model reported here offers strong negative support to the same concept.

Animals↗
PubMed1985

Generation in plasma of a fast-acting inhibitor of plasminogen activator in response to endotoxin stimulation.

Endotoxin producing bacteria cause disseminated intravascular coagulation (DIC); however, the mechanism of endotoxin action in man is still unclear. Impairment of the fibrinolytic system has been suggested as a contributing mechanism. A single injection of Escherichia coli lipopolysaccharide in rabbits resulted in a marked and prolonged increase of the levels of a fast-acting inhibitor of plasminogen activator (PA-inhibitor) in plasma (from 3.9 +/- 0.7 to 41 +/- 13.2 U/ml after 3 h). Gel filtration studies indicated that inhibition of human tissue-type plasminogen activator (t-PA) by rabbit plasma is accompanied by a change in the elution profile of the activator compatible with the formation of an enzyme-inhibitor complex with an apparent molecular weight of 100,000. Injection of human t-PA (1,500 IU/kg body wt) in endotoxin treated animals resulted in very fast inhibition of t-PA and formation of a similar complex. The half-life of circulating PA-inhibitor activity in rabbits was about 7 min as estimated by donor receiver plasma transfusion experiments. Stimulation of cultured human endothelial cells with endotoxin resulted in enhanced rate of accumulation of PA-inhibitor activity in the culture medium (two- to sevenfold increase). In five patients with septicemia, markedly increased levels of PA-inhibitor (14.3 +/- 15.5 U/ml) as compared with control subjects (1.3 +/- 0.7 U/ml) were observed in plasma. A very strong correlation (r = 0.98) was found between inhibition of t-PA and of urokinase in all conditions, suggesting that this fast-acting inhibitor reacts with both plasminogen activators. These data suggest that the appearance of this fast-acting PA-inhibitor is very sensitive to endotoxin stimulation. The marked increase in the level of PA-inhibitor in blood may contribute to the pathogenesis of DIC in septicemia.

Animals↗
PubMed1984

Identification of plasminogen activator releasing activity in the neurohypophysis.

Vasopressin (AVP) and some of its synthetic analogues, for example 1 desamino 8-D-AVP (DDAVP), induce plasminogen activator (PA) release in vivo. It has been proposed that this occurs via the release from the central nervous system of a plasminogen activator releasing hormone (PARH). The present study shows that a crude extract of bovine posterior pituitary, but not of the anterior pituitary or of the hypothalamus, induces a marked increase of circulating PA in anaesthetized rats. PA release appears to be caused by AVP because no other PA releasing activities could be identified in or isolated from the extract. In addition, no PA-releasing activity was found in extracts of pituitary glands of rats congenitally deficient in vasopressin. The following experiments did not reveal central nervous system involvement in the PA-release caused by AVP or DDAVP. Perfusion of isolated organs (rat heart and rat liver) with AVP resulted in PA-release. In squirrel monkeys, comparable PA levels were found in the venous return following intrafemoral or intracarotid injection of AVP. Moreover, when plasma obtained 2 min following AVP or DDAVP injection was transfused to a receiving animal no PA release was observed. Thus our present findings do not support the hypothesis that the fibrinolytic response to AVP is mediated by the release of a specific peptide hormone from the central nervous system.

Animals↗
PubMed1984

Influence of protein C activation on blood coagulation and fibrinolysis in squirrel monkeys.

Protein C is a circulating proenzyme which, upon activation, exerts a potent anticoagulant activity. Infusion of activated bovine protein C into dogs is accompanied by an increase of circulating tissue plasminogen activator (PA) activity. However, the evidence that human protein C shares a similar profibrinolytic capacity is still lacking. Therefore, we investigated the profibrinolytic properties of human protein C in squirrel monkeys (Samiri sciureus). Injection of activated human protein C resulted in prolongation of the activated partial thromboplastin time but was not associated with increased fibrinolytic activity of blood. Similarly, activation of endogenous protein C (up to 20-30%) by infusion of thrombin-thrombomodulin complex markedly reduced blood coagulability without being accompanied by an increase of circulating PA activity. The in vivo-generated anticoagulant activity was identified as activated protein C by the following observations. It was neutralized by rabbit anti-human protein C-IgG, was slowly inhibited by plasma but not by anti-thrombin III, was adsorbable on barium citrate, and expressed amidolytic activity. Activation of protein C appeared to be selective since other parameters such as thrombin time, platelet count, fibrinogen, and factor V levels were unaffected by thrombin-thrombomodulin infusion. Infusion of human plasma derived from whole blood incubated in vitro with human activated protein C also did not induce a fibrinolytic response, suggesting that no second messengers with PA-releasing activity were being generated in blood. It is concluded that in a primate, neither the administration of activated human protein C nor the activation of endogenous protein C are associated with an increase of fibrinolytic activity. These findings question the role of this enzyme in the regulation of PA release in man.

Animals↗
PubMed1983

Warfarin inhibits both procoagulant activity and metastatic capacity of Lewis lung carcinoma cells. Role of vitamin K deficiency.

Chronic vitamin K deficiency, either dietary or pharmacologically induced with warfarin, depressed significantly the growth of lung secondaries in a spontaneously metastasizing murine tumor, the Lewis Lung Carcinoma. This effect was associated with a marked depression of the procoagulant activity of cancer cells, which could contribute to fibrin deposition around the tumor. Cellular anticoagulation may thus be an important mechanism in the antimetastatic effect of warfarin.

Animals↗
PubMed1983

Stroke in two young siblings with congenital dysfibrinogenemia.

Two young siblings (a male of 21 and his sister of 26 years) suffered from arterial thrombosis episodes of the carotid and abdominal aorta documented by angiographic studies. In the absence of any known predisposing factor in the family and personal history, the laboratory investigation of both patients revealed coagulation abnormalities compatible with a dysfibrinogenemia. The occurrence of a similar defect also in plasma of one of the propositi's asymptomatic relatives is suggestive of an inherited fibrinogen disorder.

Adult↗
PubMed1983

Increased production of mononuclear cell procoagulant activity in Hodgkin's disease.

Procoagulant activity of peripheral blood mononuclear leucocytes was studied in 24 consecutive patients with Hodgkin's disease. Mononuclear cells, tested immediately after isolation, expressed very low activity which was, however, somewhat higher than that of cells from a matched control group (P = 0.063). Procoagulant activity generated by patients' mononuclear cells following stimulation with bacterial endotoxin was significantly higher than that produced by control cells (P less than 0.01). There was no apparent relation between procoagulant activity and pathological staging. The increased capacity of mononuclear phagocytes to produce procoagulant activity might help explain activation of blood coagulation and subsequent fibrin deposition in patients with Hodgkin's disease.

Adult↗
PubMed1983

Impaired production of mononuclear cell procoagulant activity in chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) is associated with a low incidence of thrombotic complications, or disseminated intravascular coagulation (DIC), or both, despite the frequent occurrence of severe infections. We have investigated the capacity of blood mononuclear cells to produce procoagulant activity when stimulated with bacterial endotoxin in 16 patients with untreated chronic lymphocytic leukaemia (CLL). Procoagulant activity generated by patients' cells after prolonged incubation with endotoxin was significantly lower than that produced by cells from a matched control group (p less than 0.001). The defect could not be attributed to an inhibitory effect of leukaemic lymphocytes. It is suggested that in CLL the monocyte has an intrinsic functional abnormality of the procoagulant response to endotoxin and possibly to other stimuli. These findings help explain why CLL patients do not develop thrombotic complications despite the high incidence of severe infectious diseases.

Adult↗
PubMed1983

Cultured human endothelial cells generate tissue factor in response to endotoxin.

Bacterial infection is associated with disseminated intravascular coagulation and fibrin deposition in the microcirculation; the mechanism of these effects in humans is still unclear. We have studied the generation of procoagulant activity (PCA) by cultured human endothelial cells (EC) in response to endotoxin. Cells from umbilical cord veins were grown in Eagle's minimum essential medium with 20% fetal calf serum till confluence. Absence of fibroblasts and macrophages was carefully checked. Endotoxin (Salmonella enteritidis lipopolysaccharide (LPS) W or Escherichia coli 0111:B4 LPS W, 0.01-1.0 micrograms/ml) was added to culture dishes for 4-6 h. PCA of EC was measured by a one-stage clotting assay and/or a two-stage amidolytic assay with the chromogenic substrate S-2222. In the absence of endotoxin, EC generated little, if any PCA (2-5 units/10(5) cells). In contrast, the addition of endotoxin resulted in generation of strong PCA that reached a maximum within 4-6 h (185-241 units/10(5) cells) and was dose-dependent between 1 and 0.01 microgram endotoxin/ml of culture medium. The generation of PCA required RNA and protein synthesis but did not require the presence of serum. No activity was found in the culture medium. The activity was of tissue thromboplastin type, as indicated by biological and immunological criteria. These endotoxin effects were observed in the absence of endothelial damage, as shown by phase-contrast microscopy and lack of 51Cr release. These data could contribute to elucidate the pathogenesis of vascular complications associated with endotoxemia in man.

Cells, Cultured↗
PubMed1983

Occurrence of disseminated intravascular coagulation in rat BNML leukaemia despite lack of leucocyte procoagulant activity.

Signs of disseminated intravascular clotting were observed during the development of BNML myelomonocytic leukaemia in rats, when the peripheral leucocyte count exceeded 20,000/microliters and more than 50% blasts were present in the circulation. BNML cells, harvested from blood and tested in appropriate systems, were found devoid of any procoagulant activity (PCA) even following prolonged in vitro incubation with endotoxin. Thus, it appears that these rat leukaemic cells share the same inability to express PCA which had been previously described in peripheral blood mononuclear cells from normal rats. Conceivably, in this rat model, leucocyte PCA does not represent a major trigger of intravascular coagulation and blood clotting is initiated by other, mainly plasmatic, pathways.

Animals↗
PubMed1983

Generation of procoagulant activity by mononuclear phagocytes: a possible mechanism contributing to blood clotting activation within malignant tissues.

This study investigated the procoagulant activity (PCA) of mononuclear phagocytes from rabbits bearing the V2 carcinoma. Macrophages harvested from either intraperitoneally or subcutaneously growing tumors were found to express a very strong procoagulant activity as compared with peritoneal macrophages and circulating mononuclear cells from the same animals. On the other hand, when incubated with or without endotoxin in short-term cultures, circulating mononuclear cells from tumor-bearing animals generated significantly more procoagulant activity than those from control animals. In all instances, procoagulant activity was identified as tissue factor by using assay systems with plasmas selectively deficient in the various clotting factors. These results indicate that, besides cancer cells, mononuclear phagocytes might also play an important role in the activation of blood coagulation and in the deposition of fibrin at the host-tumor interface.

Animals↗
PubMed1982

In vitro effect of endotoxin from Shigella sonnei. phase I on human blood platelets and mononuclear leucocytes: comparison of "free endotoxin" with cell-extracted preparations.

The in vitro effect of a purified endotoxin preparation from culture fluids of Shigella sonnei, phase I (purified free endotoxin, PFE) and of three endotoxin preparations chemically extracted from the intact parent cells on human blood mononuclear leucocytes and platelets was investigated. PFE, like cell-extracted preparations, caused generation of strong procoagulant activity (tissue factor) by human mononuclear cells. PFE-stimulated cells, however, developed significantly greater activity than cells stimulated by the other endotoxins. they had about 4-fold more activity. Neither free nor cell-extracted preparations induced aggregation in human citrated or heparinized platelet-rich plasma (PRP) or unmasking of platelet factor 3 (PF3). These findings suggest that free endotoxin from Shigella sonnei, phase I resembles endotoxin extracted from cells by conventional procedures in their interaction with human platelets and mononuclear leucocytes. In view of the possible contribution of free endotoxin to endotoxemia in human and experimental gram-negative sepsis, our data that free endotoxin stimulates human mononuclear leucocytes to produce a potent trigger of blood coagulation (tissue factor) may be relevant to the understanding of the mechanism(s) responsible for the initiation of intravascular coagulation in severe human infections.

Blood Platelets↗