Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human blood monocytes (Mo) and monocyte-derived macrophages (M psi) possess cytotoxic effects against tumor cell lines when appropriately stimulated by various biological response modifiers, e.g., gamma interferon (gamma IFN) and muramyltripeptide (MTP). Activated Mo/M psi represent a new tool for the treatment of human malignancies, termed "adoptive cellular immunotherapy". Activated Mo/M psi express tissue factor procoagulant activity (PCA), which is a physiological trigger of blood coagulation. PCA was evaluated in vitro using a modification of the one-stage recalcification clotting time, and hemostatic changes were studied in vivo in cancer patients. Nine patients with peritoneal carcinomatosis were injected intraperitoneally with activated Mo and 11 patients with non-small cell lung carcinomas were infused intravenously with activated M psi. Hemostatic changes were followed using activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen level, antithrombin III (ATIII) and protein C (PC) activities. Fibrinolytic activity was estimated by euglobulin lysis time and assays for plasminogen and fibrin/fibrinogen degradation products (FDP). These assays were performed before and after each autologous infusion and on days 2 and 3. Activated Mo and M psi expressed potent PCA (85.5 +/- 7.5 U/ml for MTP activated Mo and 50 +/- 5.3 U/ml for gamma IFN activated M psi suspensions). In both groups of patients, APTT, PT, and TT underwent no significant variations. There was no significant consumption of ATIII or PC, and fibrinolysis was not activated during the study period. In the group injected intraperitoneally with MTP-activated Mo, fibrinogen showed a significant and progressive increase in relation to the development of an inflammatory reaction, reaching a maximum average value of 6.1 g/l at the end of the therapy with a concomitant increase in FDP levels. This increase was not observed after intravenous therapy with gamma IFN-activated M psi. No patient suffered from hemorrhagic or thrombotic events. In our experience, repeated injections of activated Mo or M psi expressing potent tissue factor PCA did not induce significant in vivo activation of the coagulation system in cancer patients.
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PMID:Hemostatic changes in human adoptive immunotherapy with activated blood monocytes or derived macrophages. 132 42

Cisplatin, doxorubicin and daunorubicin (drugs which intercalate with DNA) influenced the membrane-bound procoagulant potential of murine thioglycollate-induced peritoneal exudate (TG-PEC) macrophages and the monocytoid cell line WEHI 265, whereas the antimetabolites 5-fluorouracil and methotrexate had no effect. Enhanced procoagulant was not caused by non-specific toxicity of these agents. Cisplatin directly increased the procoagulant expressed on WEHI 265 cells, whereas MPCA on TG-PEC was enhanced only when cisplatin was combined with a second stimulant, either bacterial lipopolysaccharide (LPS) or interferon (IFN gamma). WEHI 265 cells failed to respond to the anthracycline drugs, either alone or in combination with LPS, whereas they enhanced the IFN gamma response. Doxorubicin and daunorubicin increased the LPS response of TG-PEC by approximately 4-fold and the IFN gamma response by approximately 10-fold. Pulsing experiments suggested that the anthracyclines enhanced procoagulant expression by a mechanism different from cisplatin. Daunorubicin primed TG-PEC within 4 hr to respond to low levels of LPS, whereas either LPS or cisplatin primed these cells to respond to cisplatin or LPS respectively. Furthermore, the procoagulant expressed by TG-PEC stimulated by LPS/cisplatin had properties of tissue factor (TF: 50% total activity) and Factor VIIa (50% total procoagulant)-like activities, whereas the predominant procoagulant on LPS/anthracycline activated TG-PEC was TF-like (70% total activity) with weak Factor VIIa and prothrombinase-like properties.
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PMID:Induction of macrophage procoagulant expression by cisplatin, daunorubicin and doxorubicin. 212 Jan 34

Monocytes and endothelial cell interactions play a key role in the development of vascular lesion, inflammation and atherosclerosis. Leukocyte adhesion is mediated through specific molecules CD11/CD18 complexes on the leukocyte side and the ELAM (Leukocyte Adhesion Molecule) ICAM (Intercellular Adhesion Molecule) on the endothelium cell surface. Several monocyte products damage endothelial cells such as free radicals, oxygen peroxides, proteases, hydrolases, lipases... Various monokines alter endothelial cell function and proliferation. Interleukin 1, gamma interferon, alpha tumor necrosis factor increase ELAM, further more they induce the synthesis of procoagulant activity by endothelial cells. Monocyte derived growth factor stimulates endothelial cells proliferation while transforming growth factors, beta (TGF beta) and TNF alpha inhibit endothelial cell growth. Lipid products of monocyte origins such as leukotrienes induce an activation of endothelial cells which results in a production of prostacyclin. Monocytes may also participate in the coagulation process by producing thromboplastin and coagulation factors and facilitating the tenase (activation of factor X) complex formation. On the other hand, monocyte also synthesize tissue plasminogen activator and inhibitor. The numerous factor produced by monocytes may affect in different ways the endothelial cell behavior.
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PMID:[Monocyte-endothelium relations]. 265 10

Recombinant gamma-interferon (r gamma-IFN) has contrasting effects on thromboplastin (TPL) synthesis induced in monocytes (M) and endothelial cells by bacterial lipopolysaccharide (LPS), phorbol ester (TPA), and phytohaemagglutinin (PHA). In human umbilical vein endothelial cells (HUVEC) the induced thromboplastin response was significantly augmented by r gamma-IFN whereas the monocyte response was inhibited. Recombinant alpha-interferon (r alpha-IFN) had no effect on thromboplastin induction in endothelial cells but had a significant inhibitory effect on the TPL response in monocytes when LPS or LPS and cyclosporin A (CS) were used as inducing agents. Cyclosporin A, previously shown to enhance thromboplastin synthesis induced in monocytes, also contributes to a higher level of thromboplastin activity in endothelial cells. Its effect on monocytes was in most cases fully inhibited by r gamma-IFN (and also by r alpha-IFN when tested). gamma-Interferon and alpha-interferon alone had a weak stimulatory effect or none on thromboplastin synthesis in both cell types.
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PMID:Differential effect of alpha-interferon and gamma-interferon on thromboplastin response in monocytes and endothelial cells. 312 8

Alpha-2 interferon, produced in Escherichia coli using recombinant DNA techniques, was administered to 17 children with refractory acute lymphoblastic leukemia (ALL) in relapse, two children with TdT-positive, Philadelphia chromosome-positive chronic myelocytic leukemia (CML) in blast crisis, and one child with B cell (SIg+) non-Hodgkin's lymphoma (NHL) in a second extramedullary relapse. An initial 2-week intravenous (IV) phase of interferon was followed by a 3-month subcutaneous (SC) maintenance phase if patients had an objective response or disease stabilization without significant bleeding or infectious complications. When interferon dosages were escalated from 3 to 100 X 10(6) U/m2 in the first phase of therapy, there was rapid progression of disease in the first four patients treated, prompting a modification of the treatment plan. The last 16 patients enrolled received fixed dosages of interferon (ie, 10, 20, 30, and 50 X 10(6) U/m2 administered to four subjects each). One child with T cell ALL had an 11-month complete remission; the patient with lymphoma had a dramatic but brief response; three others (one CML and two ALL) showed disease stabilization for 3 to 6 months with a definite oncolytic effect in two of the three patients. The remaining 15 patients had progressive disease within 2 months and were removed from the study. Acute toxicity included a flu-like syndrome in all patients, increased serum transaminase levels in five, seizures in three (two cases temporally related to fever and one to a thrombocytopenic subarachnoid hemorrhage), and prolonged activated partial thromboplastin times in seven. This phase I-II trial of recombinant alpha-2 interferon demonstrated definite activity without dose-limiting toxicity.
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PMID:Phase I-II study of recombinant alpha-2 interferon against advanced leukemia and lymphoma in children. 345 76

Seven patients with myeloblastic leukemia were treated for 10 days with high-dose (15 or 30 million units/m2/day), human lymphoblastoid interferon (Wellferon) by continuous iv infusion. All patients developed prolonged activated partial thromboplastin time, and four developed prolonged prothrombin time. Factor assays demonstrated low levels of II, VII, IX, X, and XII. Coagulation abnormalities improved after discontinuation of interferon therapy.
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PMID:Coagulopathy induced by continuous infusion of high doses of human lymphoblastoid interferon. 385 79

A rabbit antiserum against an 18- to 27-kD native protein fraction (F3) from Eimeria acervulina merozoites identified a cDNA (3-1E) containing a 1086-base pair insertion with an open reading frame of 170 amino acids (predicted molecular weight, 18,523). The recombinant 3-1E cDNA expressed in Escherichia coli produced a 60-kD fusion protein and a 23-kD protein after factor Xa treatment of the fusion protein. Both proteins were reactive with the F3 antiserum by western blot analysis. A rabbit antiserum against a synthetic peptide deduced from the amino acid sequence of the 3-1E cDNA reacted with a 27-kD recombinant 3-1E protein expressed in Sf9 insect cells and a 20-kD native protein expressed by E. acervulina sporozoites and Eimeria tenella sporozoites and merozoites. By immunofluorescence staining, a monoclonal antibody produced against the recombinant 3-1E protein reacted with sporozoites and merozoites of E. acervulina, E. tenella, and Eimeria maxima. Spleen lymphocytes from E. acervulina-immune chickens showed antigen-specific proliferation and interferon (IFN)-gamma production upon stimulation with the recombinant 3-1E protein, indicating that the protein activates cell-mediated immunity during coccidiosis. Immunization of chickens with either the E. coli- or Sf9-expressed recombinant 3-1E protein with adjuvant, or direct injection of the 3-1E cDNA, induced protective immunity against live E. acervulina. Simultaneous injection of the recombinant 3-1E protein, or the 3-1E cDNA, with cDNAs encoding chicken IFN-gamma or interleukin (IL)-2/15 further enhanced protective immunity. These results indicate that the recombinant E. acervulina 3-1E cDNA or its polypeptide product may prove useful as vaccines against avian coccidiosis.
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PMID:A recombinant Eimeria protein inducing interferon-gamma production: comparison of different gene expression systems and immunization strategies for vaccination against coccidiosis. 1087 19

The spontaneous loss of normal karyotype embryos may be initiated or prevented by the maternal immune system. In mice, loss between the time of implantation (day 4.5) and formation of a vascularized placenta (day 9.5) when the embryo is too large to survive by diffusion alone, is analogous to occult pregnancy failure in humans. They are called occult because usually the woman does not know she is pregnant. From studies in mice, these early losses have a different mechanism than abortion of a vascularized placenta (analogous to clinically evident human spontaneous miscarriage). The latter depend on the activation of the novel prothrombinase fgl2 on the fetal trophoblast and in maternal decidua by the T helper-1 (Th1) type cytokines TNF- alpha+gamma -interferon that arise from NK cells and NK gammadelta T cells; conversion of prothrombin to thrombin which in turn generates IL8 that activates polymorphonuclear leukocytes leads to embryonic death. These inflammatory processes are counteracted by Th2/3-type cytokines that arise in part from V gamma 1 delta 6 T cells reacting to, as yet, unidentified trophoblast antigens in the presence of the 'tolerance signaling molecule' OX-2. By contrast, peri-implantation losses (between implantation and formation of a vascularized placenta, analogous to occult losses in humans) appear to be dependent upon perforin(+)cells, complement activation, and products of alphabeta T and NK alphabeta T cells, but not on TNF- alpha or procoagulant activation. Similarities and differences between findings in the mouse and human, and the potential evolutionary significance of mechanisms affecting reproductive success are reviewed.
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PMID:Procoagulants in fetus rejection: the role of the OX-2 (CD200) tolerance signal. 1143 33

We describe a young woman who developed acquired haemophilia after 18 months of interferon (IFN-)-alpha therapy. This patient had been monitored since 1992 for Hodgkin's disease initially treated by chemotherapy. After two relapses, she received intensive chemotherapy followed by an autologous peripheral progenitor cell graft. IFN-alpha was then administered for 18 months. Bleeding of the limbs and tongue occurred 1 month after withdrawal of IFN-alpha and high titres (123 Bethesda units) of autoantibody to factor VIII (FVIII):C were measured. Prednisone (1 mg kg(-1) day(-1)) achieved rapid cessation of the bleeding and FVIII autoantibodies were undetectable 5 months later. This case report suggests that the activated partial thromboplastin time should be regularly checked in every patient treated with IFN-alpha in cases of unexplained bleeding, together testing for antibodies to FVIII if the bleeding is prolonged.
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PMID:Acquired inhibitor to factor VIII in a patient with Hodgkin's disease following treatment with interferon-alpha. 1155 46

Chronic liver disease is accompanied by derangement of hepatocyte function including the synthesis of haemostastic factors. It is, however, not known whether the improvement in liver functions as a result of interferon (IFN)-alpha therapy would be reflected in the plasma levels of these factors. To evaluate the effect of IFN-alpha therapy on the plasma levels of natural anticoagulants and on the fibrinolytic parameters, in patients with chronic viral hepatitis. Twenty one patients with chronic viral hepatitis (B and C) were treated with IFN-alpha, and were studied before commencement of therapy (first sample) 3 (second sample) and 6 months (third sample) later. The coagulation screening tests: activated partial thromboplastin time, prothrombin time, thrombin time, reptilase time and plasma fibrinogen and the natural anticoagulants: antithrombin, Protein C and free and total protein S as well as fibrinolytic parameters (tissue type plasminogen activator, plasminogen activator inhibitor type-1 and plasminogen) were measured. An increase in the levels of total protein S at 3 and 6 months after the commencement of IFN therapy was noted but the increase was statistically significant in the latter period. Reptilase time was prolonged in the first (pretreatment) and in the second samples and then began to decrease in the third sample but remained higher than the pretreatment level. Fibrinogen level increased in the second and third samples. No remarkable changes were noted in other haemostatic parameters. Total protein S level is a good marker of response to IFN therapy. IFN therapy does not affect other natural anticoagulants or fibrinolytic parameters. More detailed studies need to be done to confirm these findings.
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PMID:Natural anticoagulants and fibrinolytic activity following interferon therapy in chronic viral hepatitis. 1846 46


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