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Biomedical subjects

M C Boffa

Publications and source records attributed to M C Boffa.

At least 19 recordsLinked to original sources
PubMed1995

[Antiphospholipid antibodies: cause of thrombosis or an epiphenomenon?].

Antiphospholipid antibodies (aPL) present in systemic lupus erythematosus and the primary antiphospholipid syndrome are a well-known risk factor for thrombosis. Most of them require the presence of a cofactor, beta 2-glycoprotein I for anticardiolipin antibodies, prothrombin for lupus anticoagulant. These aPL are of the "immune" type. APL are also found in various non-immunological conditions, in which repeated endothelial or membranous damages appear to be frequent, but thromboses are rare. Most of these aPL are cofactor-independent, except those induced by chlorpromazine, and might belong to "natural" antibodies.

Animals↗
PubMed1994

Plasma thrombomodulin in orthotopic liver transplantation.

Plasma thrombomodulin (TM), a specific marker of vascular endothelial injury was measured pre-, per-, and postoperatively in 16 consecutive patients undergoing orthotopic liver transplantation (OLT). The TM level, which was already elevated preoperatively, remained unchanged during OLT, except for an acute and transitory spike at the time of graft reperfusion. This TM peak is probably attributable to an acute release from the patient's endothelium because the TM level in the last saline rinse of the graft before implantation was low. This TM spike was not correlated with the progressive tissue-type plasminogen activator (t-PA) increase, plasminogen activator inhibitor 1 (PAI-1), or von Willebrand factor (vWF) values. The absence of accumulation of TM in plasma, unlike that of t-PA, suggests that the liver does not play a major role in TM clearance in humans. At the end of surgery, individual TM values returned to preoperative levels and remained unchanged during the 7 days following surgery. This observation suggests that the high (or very high) TM levels measured in these patients might be due to an indirect rather than a direct effect of liver dysfunction on the vascular endothelium which remained damaged during the postoperative period. The possibility that TM might be a predictive marker for thrombotic OLT complications remains to be investigated in a postoperative follow-up study.

Adolescent↗
PubMed1994

Design and validation of a new immunoassay for soluble forms of thrombomodulin and studies on plasma.

Thrombomodulin (TM), purified from human placental homogeneate by affinity chromatography on DIP-Thrombin agarose, was used to develop monoclonal antibodies (MAbs). Two of them, 3E2 and 24FM (both IgG1, K), which were not calcium-dependent, were found convenient for developing a two-site enzyme immunoassay. Testing of recombinant and truncated forms of TM26 demonstrated that the species containing the amino terminus including the lectin-like domain and the epidermal growth factor (EGF)-like domains 1-4 were fully measured. The working range was from 2 to 100 ng/ml with a detection threshold of 2 ng/ml. Intraassay and interassay reproducibilities were, respectively, below 7.4% and 8.6%, whereas recovery of purified TM was between 88 and 114% in plasma. Mean plasma concentration was 42.1 (+/- 11.3) ng/ml (males 51.8 +/- 7.9 ng/ml, females 34.8 +/- 7.8 ng/ml) and it was established on 62 normal individuals between the ages of 21 and 55 (28 males and 34 females). This new assay is a convenient tool for measuring plasma TM and establishing its diagnostic and predictive value in diseases associated to endothelial damage.

Adult↗
PubMed1994

Plasma thrombomodulin level in malignancy varies according to the tumor type.

Plasma thrombomodulin (TM) level was measured by ELISA in patients with either digestive tract cancers or malignant melanomas. A striking difference was seen between tumor types with an increase in the TM level of the former and a decrease in the latter. This finding is in agreement with the classification of tumors previously proposed by Zacharski et al.

Digestive System Neoplasms↗
PubMed1993

Platelet hyperactivation in patients with essential thrombocythemia is not associated with vascular endothelial cell damage as judged by the level of plasma thrombomodulin, protein S, PAI-1, t-PA and vWF.

The occurrence of thrombotic events remains an important clinical problem in Essential Thrombocythemias (ET). Thus, hemostatic, fibrinolytic and vascular status was investigated in 16 patients (5 males and 11 females) with ET. Among them five presented thromboses in their past history. Platelet hyperactivation, as evidenced by a mean three-fold increase in plasma betathromboglobulin (beta TG), was observed in 13 among 16 patients; surprisingly this activation was present even when the platelet count was normal (in two patients) or subnormal, below 600 x 10(9)/l (in 11 patients). The mean value was 104 +/- 57 IU/ml significantly different from that of normal controls (35 +/- 16.5 IU/ml) (p < 0.001). An artefactual in vitro platelet activation was ruled out by the concomitant measurement of platelet factor 4 (PF4). D-dimers fibrin degradation products (D-Di FDP) were normal in all patients. Vascular endothelial cell function parameters were not markedly modified. The mean value of plasma thrombomodulin (TM) was found slightly but not significantly increased (60.1 +/- 4.9 ng/ml versus 49.1 +/- 10.0 ng/ml in controls). The values of plasma TM correlated neither with that of the platelet count nor with that of plasma beta TG or plasma PF4. The mean values of plasma protein S, von Willebrand factor (vWF), plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (tPA) were normal and were not correlated neither with that of plasma TM nor with that of plasma beta TG.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Demonstration of Rickettsia conorii-induced endothelial injury in vivo by measuring circulating endothelial cells, thrombomodulin, and von Willebrand factor in patients with Mediterranean spotted fever.

The endothelial cell (EC) is the primary target for Rickettsia conorii (RC) in Mediterranean spotted fever (MSF). Clinical manifestations such as thrombosis and vasculitis are mediated by pathologic changes localized in blood vessels. To study the in vivo endothelial injury induced by RC, markers of endothelial damage, including circulating EC (CEC), plasmatic thrombomodulin (TM), and von Willebrand factor (vWF), were investigated in 12 patients with MSF. CEC were counted in whole blood by a new immunomagnetic separation assay using a specific anti-EC antibody, S-Endo 1. Plasmatic TM and vWF antigens were measured by enzyme-linked immunosorbent assay. High levels of CEC and cell fragments were found in patients with a severe or malignant form of MSF. Sequential studies of CEC showed a decrease from 162 +/- 454 cells/mL before treatment to 6 +/- 7 cells/mL during treatment and recovery. Mean plasma TM and vWF levels that were also elevated before therapy (TM, 106 +/- 27 ng/mL; vWF, 420% +/- 164%) decreased progressively (TM, 55 +/- 43 ng/mL; vWF, 148% +/- 26%) during treatment. The measurement of cellular and molecular markers of vascular damage such as CEC, plasmatic TM, and vWF contributes to the definition of the Rickettsia-induced endothelial injury in vivo.

Antibodies, Monoclonal↗
PubMed1993

Increased plasma thrombomodulin in cancer patients.

Plasma samples from 35 patients with colorectal cancer, 16 patients with pancreatic cancer and 46 patients with various cancers in the terminal stage were analysed for soluble plasma thrombomodulin with an ELISA method. At time of diagnosis and before primary treatment, the patients with colorectal cancer had normal plasma TM levels. In the patients who developed disseminated disease, the mean plasma TM level increased significantly. In the patients with pancreatic cancer, the mean plasma TM level was increased already at time of primary treatment. The TM level increased further with progress of the pancreatic cancer. In the patients with various cancer types in the terminal stage, the mean TM was also significantly increased compared to healthy controls. Great individual variation in the plasma TM level was observed, as well as great variation of mean TM level between the various cancer types. There was no significant correlation between the TM levels and the levels of tissue factor pathway inhibitor, another endothelial coagulation inhibitor, which increased with progress of malignant disease. This may indicate different underlying mechanisms for the increased plasma levels.

Adenocarcinoma↗
PubMed1993

Antiphosphatidylethanolamine antibodies in systemic lupus erythematosus.

Antiphosphatidylethanolamine antibodies (aPEA) were investigated in a population of 78 systemic lupus erythematosus (SLE) patients, by means of an enzyme-linked immunosorbent assay method. These antibodies are specifically directed against phosphatidylethanolamine, one of the zwitterionic phospholipids present in cell membranes. Antiphosphatidylethanolamine antibodies were found in 13 patients (16.6%). They were generally associated with lupus anticoagulant (two patients), antiphospholipid antibodies directed against anionic phospholipids (six patients), or both (four patients). In only one case, aPEA were the sole detectable antiphospholipid antibodies. Thrombosis, recurrent fetal loss, valvular disease or neurological involvement was present in most (11 of 13) of the patients with aPEA. It seems valuable to carry on further searches for these antibodies in SLE, since patients with aPEA are at higher risk of thrombosis and/or recurrent fetal losses than are patients with antiphospholipid antibodies (anticardiolipin, anti-anionic phospholipid and/or lupus anticoagulant) other than aPEA. Moreover, since aPEA can be the sole detectable antiphospholipid antibodies, they should be investigated in SLE with thrombosis when neither lupus anticoagulant nor anticardiolipin antibodies can be demonstrated.

Adolescent↗
PubMed1993

Plasma reactivity to hexagonal II phase phosphatidylethanolamine is more frequently associated with lupus anticoagulant than with antiphosphatidylethanolamine antibodies.

In membranes, phosphatidylethanolamine (PE) is usually in a lamellar phase, but it can also adopt a hexagonal II phase (HexII PE), which has been demonstrated to be immunogenic in mice and has recently been used in a new clotting assay to detect lupus anticoagulant (LA). A population of 58 patients susceptible of having LA or antiphospholipid antibodies (aPLA), was screened for reactivity to HexII PE using the new clotting assay and for the presence of anti-PE antibodies (aPEA) using ELISA. The patients could be classified as follows: 26 systemic lupus erythematosus, 14 primary antiphospholipid syndromes and 18 miscellaneous non autoimmune disorders. HexII PE reactivity was detected in 22 patients. It was significantly more often associated with LA-positivity (20/29) than with LA-negativity (2/29), (p < 0.0001). However, 9 patients with LA had negative HexII PE assays. Anti-PE antibodies were detected by ELISA in only 12% of the cases. No correlation was observed between the distribution of aPEA and that of HexII PE reactivity. Interestingly, 2 LA- and aPLA-negative patients exhibited HexII PE reactivity. The absence of identity between the distribution of HexII PE reactivity and that of either LA or aPEA indicates that this new assay has its own specificity. It might detect antibodies to the immunogenic hexagonal PE and may therefore have a broader scope than that proposed initially. Although in the studied populations, no significant relationship could be found between HexII PE positivity and clinical complications (thrombosis and/or recurrent fetal losses), it might be associated with other complications of the antiphospholipid syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗