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Biomedical subjects

M Mirshahi

Publications and source records attributed to M Mirshahi.

At least 91 records · Page 5Linked to original sources
PubMed1989

Evaluation of the inhibition by heparin and hirudin of coagulation activation during r-tPA-induced thrombolysis.

Thrombin bound to a fibrin clot remains active and poorly accessible to heparin-AT III complex. During fibrinolysis, thrombin is released as thrombin-FDP complex and is inactivated by heparin-AT III. However, as successive fibrin layers are removed, inaccessible molecules of thrombin are exposed at the surface of the residual clot, possibly contributing to the occurrence during thrombolytic therapy of coagulation that is poorly controlled by heparin. We have investigated the accessibility of fibrin-bound thrombin to hirudin. The results clearly show that two recombinant hirudin variants neutralize thrombin both in solution and fibrin bound. Furthermore, we have found that in in vitro models, hirudin present in the surrounding medium of a clot under lysis is more efficient than heparin in preventing the activation of coagulation. This observation suggests that hirudin may be effective in the prevention of the rethrombotic process frequently encountered during thrombolytic therapy.

Adsorption↗
PubMed1989

Production of proteases type plasminogen activator and their inhibitor in cornea.

Corneal epithelial cells secrete tissue plasminogen activator (t-PA), urokinase type plasminogen activator (u-PA) and their inhibitor (PAI), whereas these cell types in other tissues are known to secrete only u-PA hitherto. Endothelial cells in the cornea produce mostly u-PA and only small amounts of t-PA and PAI which remain confined in the cellular compartment contrary to the situation in the vascular endothelial cells where they are liberated into the circulation in the order PAI greater than t-PA greater than U-PA. These unique features of activator/inhibitor secretion and production may play an important role in the remodeling of the corneal matrix.

Animals↗
PubMed1988

High frequency of plasminogen activator secretion by malignant human lymphoid cell lines of T-cell type origin.

Diffuse defibrination is rarely observed in acute lymphoblastic leukemia (ALL). Clinical and immunologic data suggest that it is more likely to occur in T cell derived ALL. The current investigation involved the secretion of plasminogen activators (PA) of tissue type (t-PA) or urokinase type (U-PA) by testing supernatants of 21 permanent human leukemic cell lines originating from various hematopoietic lineages and one induced lymphoblastoid cell line. (LCL) The amount of PA in each supernatant was determined by biologic and immunoenzymologic assays. The correspondence with the expected molecular weight (MW) according to the PA type was checked by zymography. PA secretion of U-PA type was observed in the three myeloid cell lines. Except for the normal LCL, no B-lymphoid lineage related cell lines of various levels of differentiation displayed PA secretion, whereas PA activity was observed in the supernatant of six of nine malignant T-cell lines. The T-leukemic cell lines CCRF CEM, KE 37, HUT 78, and HUT 102 released U-PA-like activity. Peer released t-PA-like activity and CCRF-HSB2 supernatant showed both types of PA activity. These findings are discussed in view of the natural history of these diseases and the stage of differentiation of the cell lines.

Humans↗
PubMed1988

Parallel induction of fibrinolysis and receptors for plasminogen and urokinase by interferon gamma on U937 cells.

A new cell sorter technique was employed to study the role of interferon gamma (INF gamma) in fibrinolysis induced by U937 monocytic cells. INF-gamma induced the differentiation of U937 cells as evidenced by the appearance of CD 14 antigen on the cell surface. Scatchard analysis and dose response curves showed a parallel increase in the number of receptors on U937 cells capable of accepting exogenous plasminogen and urokinase (UPA) synthetized by differentiating U937 monocytic cells. This would favour an activation of plasminogen by UPA. This adds a new parameter in the regulation of cell-mediated fibrinolysis and may be important in a number of biological processes.

Cell Line↗
PubMed1988

Changes in plasma fibrin degradation products as a marker of thrombus evolution in patients with deep vein thrombosis.

The level of fibrin degradation products (fdp) as a marker of fibrin clot dissolution was studied prospectively in 51 patients with phlebographically identified deep vein thrombosis (DVT). For this purpose a highly sensitive fdp assay using an anti D neo monoclonal antibody (McAb) was used. At the onset of the hospitalization, in 47 (92%) of the 51 patients tested, the plasma fdp level performed was high, but does not reflect the size of the thrombus, demonstrating that spontaneous thrombus lysis varies from one patient to another. During 10 days of standard heparin or low molecular weight heparin treatment, two different patterns of fdp evolution could be identified in these patients, independent of the type of heparin used. The first was characterized by a gradual decrease in fdp level and a corresponding reduction in the thrombus size. The second pattern showed a persistence of high levels of fdp after 10 days of therapy although the phlebographic score reveals a poor or partial response indicating that fibrinolysis or the balance of thrombus formation/fibrinolysis did not insure total thrombus dissolution. The 4 patients whose initial plasma fdp levels were only slightly increased during the 10 days, seem to have poor thrombolysis, as was shown by the unmodified phlebographic score after 10 days of treatment. Consequently, we conclude that the investigation of plasma fdp levels with a highly sensitive assay should contribute to the evaluation of thrombus evolution in DVT.

Enzyme-Linked Immunosorbent Assay↗
PubMed1988

Enhanced expression of urokinase activity on U 937 cell line by 1,25-dihydroxyvitamin D3 induction.

1,25 Dihydroxyvitamin D3 is a differentiation inducer for monocytic cell. It can induce a monoblastic cell line U937 to differentiate. In this paper, we report that by inducing the differentiation of U937, 1,25-dihydroxyvitamin D3 increased urokinase activity expression on U937 cell surfaces. After incubation of the cell with various concentrations of 1,25-dihydroxyvitamin D3, the cell line showed a remarkable progressively increasing membrane-associated urokinase activity in a dose dependent manner. On the contrary, plasminogen activator inhibitor activity which was found in the culture medium is not modified by the 1,25-dihydroxyvitamin D3 induction. This results suggests another role of 1,25-hydroxyvitamin D3 in the treatment of myelofibrosis, since enhanced plasmin generation can accelerate the activation of procollagenase. The induced plasmin and collagenase activities surrounding the monocytic cells may participate in the physiological and pathological events, especially in the connective tissue degradation.

Calcitriol↗
PubMed1988

Defective thrombolysis due to collagen incorporation in fibrin clots.

The migration of fibroblasts into a clot may be responsible at least in part, for its organization, thus leading to a defective thrombolysis. We have shown that collagen incorporated in a fibrin clot induces a dramatic decrease in fibrinolysis. Despite the fact that plasminogen binds to collagen, tissue plasminogen activator induced plasminogen activation in the presence of fibrin is only slightly decreased by the presence of collagen. This rather suggests that collagen induces a modification in clot structure, by rendering fibrin less accessible to fibrinolytic enzyme.

Animals↗
PubMed1987

Glycosylation of human fibrinogen and fibrin in vitro. Its consequences on the properties of fibrin(ogen).

As observed for many proteins, glucose has been shown to bind non enzymatically to fibrinogen and to fibrin. The in vitro degree of glycosylation depends upon the concentration of glucose added to fibrinogen and also on the incubation period. This glycosylation induces a decrease in fibrin lysis by plasmin. On the contrary, it does not influence either fibrinogen activity as cofactor in ADP-induced platelet aggregation or the binding of thrombin onto a clot. Despite the 4 day half life of fibrinogen, since clearance of fibrinogen is exponential, it is assumed that very small quantities of fibrinogen may remain for a long time in the circulation leading to the presence of a low level of a highly glycosylated form of fibrinogen. Consequently, poorly degradable fibrin might be derived from this highly glycosylated fibrinogen and thus be responsible for capillary occlusion and also for atherosclerotic complications in the diabetic patient.

Adenosine Diphosphate↗
PubMed1987

Dynamic coronary fibrinolysis evaluation in patients with myocardial infarction and unstable angina by specific plasma fibrin degradation product determination.

It has been shown that myocardial infarction (MI) is caused by thrombotic occlusion of a coronary artery. A thrombotic process is also involved in the flow obstruction associated with peripheral embolization in unstable angina (UA). In UA, a local fibrinolytic process should occur, but biological evidence has never been reported. Therefore, we measured sequential changes in plasma fibrin degradation products (FDP) in patients with stable and unstable angina pectoris without MI and compared the levels to those in patients with MI. FDP determination was carried out by ELISA using a D neo monoclonal antibody allowing low amounts of FDP to be reliably and precisely detected. Our results show an early increase in FDP in UA indicating a thrombolytic process. In patients who presented only one episode of chest pain, a prompt decrease of FDP was noted whereas in patients with recurrent chest pain, the levels of FDP remained high. On the contrary, during the first 3 days of uncomplicated MI, FDP levels were not significantly different from those of normal control suggesting an absence of clot dissolution. This study underlines the important function of fibrinolysis in the spontaneous evolution of acute coronary syndrome.

Angina Pectoris↗
PubMed1987

Prevention of experimental autoimmune uveoretinitis by active immunization with autoantigen-specific monoclonal antibodies.

Preimmunization of Lewis rats with anti-S antigen (S-Ag) monoclonal antibodies (mAb) led to protection against experimental autoimmune uveoretinitis (EAU) induced by this retinal autoantigen. High titers of anti-idiotypic (anti-Id) antibodies were raised against three mouse mAb, S2D2 (IgG2b), S6H8 (IgG2a) and S7D6 (IgG1), directed at S-Ag. An almost complete prevention was observed in S2D2 mAb-immunized animals while a partial protection was achieved with S6H8 and S7D6 mAb. No detectable anti-Id antibody nor disease prevention was observed in rats immunized with the mAb S9E2 (IgG2a) which only recognizes bovine and sheep S-Ag, or with control mAb of the same isotypes irrelevant to S-Ag. The mAb treatment did not modify the level of the whole polyclonal antibody response to S-Ag. These results suggest an important role in the pathogenesis of EAU for the epitopes recognized by S2D2-S6H8 and S7D6 in the S-Ag molecule. The success of anti-Id immunization for autoimmune disease suppression may depend on the identification of relevant epitopes.

Animals↗
PubMed1987

Specific determination and identification of cross-linked fibrin degradation products in patients under thrombolytic therapy for myocardial infarction.

We have demonstrated that the specific determination and identification of plasma FbDP alone is not sufficient to follow the effectiveness of thrombolytic therapy. Some patients who received an intravenous infusion of rt-PA for myocardial infarction had very high plasma FbDP levels, although no recanalization was observed angiographically. Since in many cases the FbDP levels increased after recanalization, it is assumed that rethrombosis may occur during and after t-PA treatment.

Antibodies, Monoclonal↗
PubMed1987

[Importance of the structure of the clot in thrombolysis].

Activation of plasminogen by tissue-type plasminogen activator (tpA) is potentiated by fibrin. We have demonstrated the role of fibrin polymerization in the potentiating effect of tpA-induced fibrinolysis. Therefore a pathogenic mechanism of thrombotic disorder may be related to an abnormal fibrin polymerization: the abnormal clot being less accessible to fibrinolysis than normal one. This defective lysis may be due to a defective enhancement by the abnormal fibrin of plasminogen activation by tpA, as demonstrated for fibrinogen Dusard, a congenital dysfibrinogenemia associated with a very severe thrombotic disorder. In some other cases, a decrease in the availability of the plasmin cleavage sites in fibrin clot may be involved. On the contrary, some antithrombotic drugs such as pentosane polysulfate in modifying clot structure allow a better degradation of fibrin clot by fibrinolytic enzymes. It is speculated that this enhanced fibrinolysis could explain, almost in part, the antithrombotic action of these drugs.

Blood Coagulation↗
PubMed1987

[A specific marker of thrombolysis: DDE complex].

A specific determination of fibrin degradation product (FbDP) is essential for the monitoring of thrombolytic therapy. In patients under thrombolytic therapy, even with tpA (tissue type plasminogen activator) fibrinogen is degraded, and fragment D derived from fibrinogen degradation, is evidenced in the plasma of treated patients. In order to determine specifically the FbDP, even in the presence of fragment D, we take into account the fact that FbDP are complexes such as DDE complex. Therefore a new Elisa technique is proposed. FbDP and fragment D are captured from plasma by immobilized anti D neo monoclonal antibody which recognizes an epitope accessible on fragment D but does not react with undegraded fibrinogen. DDE complexes are then detected specifically using a peroxidase-labelled anti E antibody. The advantage of this technique is discussed in this paper.

Antibodies, Monoclonal↗
PubMed1987

[Identification of a protein related to the S-antigen in choroid plexus in quails].

Using monoclonal and polyclonal antibody immuno-fluorescence, various areas of the quail diencephalon were tested immunocytochemically for the presence of S-antigen, which is a regulatory protein of retinal photoreceptors. In adult quail and embryos (from day 13 until hatching), S-antigen immunoreactivity was demonstrated in the cytoplasm of epithelial cells in the choroid plexus of the third ventricle. Similar data have previously been obtained in quail retinal photoreceptors. No labeling could be seen in the other investigated diencephalic areas, including the hypothalamus. Although an extraocular photoregulation of the reproductive cycle has previously been reported in birds, further investigations are needed before it can be concluded that the choroid plexus of the third ventricle is involved in this or other types of regulation.

Animals↗
PubMed1986

A latex immunoassay of fibrin/fibrinogen degradation products in plasma using a monoclonal antibody.

We have developed a latex immunoassay using an anti D neo monoclonal antibody (F2C5) which recognizes an epitope present in fragment D but which is hidden in intact fibrinogen and in early fibrinogen degradation products. This technique was applied directly to plasma of both healthy donors and patients, and was shown to be very convenient for clinical investigation, especially in emergency cases for diagnosis of intravascular coagulation. The use of plasma samples instead of serum offers several advantages: it is not time consuming since blood clotting is not required; it avoids overestimation when fibrinogen cannot be totally clotted, and underestimation due to the binding of nonclottable fibrin degradation products to the clot during clotting in vitro. This monoclonal antibody, which reacts more with FbDP (expressed in fragment D) than with fragment D, does not allow fibrin and fibrinogen degradation products to be differentiated. However, this discrimination does not seem critical for its clinical use since the level of fragment D neo antigen remained within the normal range in 12 cases of spontaneous or venous occlusion-induced hyperfibrinolysis.

Antibodies, Monoclonal↗
PubMed1986

Expression of the photoreceptor-specific S-antigen in human retinoblastoma.

This work presents an immunofluorescent study of the distribution of the photoreceptor-specific S-antigen in human retinoblastoma, using mouse monoclonal antibodies. Three cases of differentiated retinoblastoma displayed S-antigen immunoreactivity with various patterns of labeling which depended on the degree of differentiation of the area studied. Flexner-Wintersteiner rosettes and fleurettes were labeled only with monoclonal antibody S2D2, whereas undifferentiated areas were labeled with four different anti-S-antigen monoclonal antibodies, including S2D2. On the other hand, the three undifferentiated retinoblastomas did not show any labeling with these antibodies. The presence of S-antigen in differentiated retinoblastoma confirms that the origin of this tumor is from the photoreceptors, but the question remains unanswered for undifferentiated retinoblastoma for which another origin--glial or primitive neuroectodermal cells--may be proposed.

Antibodies, Monoclonal↗