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  • 1
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    HLA associations with leukemia (1987)
    American Society of Hematology
    Details
    Publication Date: 1987-07-01
    Description: Frequencies of 35 HLA A, B, C, and DR antigens were determined in 1,834 leukemic Caucasoids to evaluate possible associations between HLA and leukemia. In comparison with the frequencies of HLA antigens in published controls, the frequency of Cw3 was significantly higher in patients with acute lymphoblastic leukemia (relative risk = 2.64, P less than 0.0002), acute myelogenous leukemia (relative risk = 1.92, P less than 0.0007), and chronic myelogenous leukemia (relative risk = 2.07, P less than 0.002; P values adjusted for multiple comparisons). The frequency of Cw4 was elevated in patients with acute lymphoblastic leukemia (relative risk = 2.01, P less than 0.0003), acute myelogenous leukemia (relative risk = 2.06, P less than 0.0002), and chronic myelogenous leukemia (relative risk = 2.14, P less than 0.0008). The frequency of Aw19 was significantly decreased in patients with acute myelogenous leukemia (relative risk = 0.68, P less than 0.01) and chronic myelogenous leukemia (relative risk = 0.59, P less than 0.005). None of the other 32 HLA antigens investigated had a statistically significant association with leukemia. The data suggest that Cw3 and Cw4 may be markers for leukemia susceptibility genes, while Aw19 may be a marker for decreased susceptibility to leukemia.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 2
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    Large granular lymphocyte proliferation: an analysis of T-cell receptor gene arrangement and expression and the effect of in vitro culture with inducing agents (1988)
    American Society of Hematology
    Details
    Publication Date: 1988-01-01
    Description: The status of the T cell receptor beta and gamma genes in natural killer (NK) cells was investigated in two patients with a marked expansion of CD2+, CD3- NK cells. Both genes were found to be in the germline state. The T alpha and complete T beta gene transcripts were not detected, but a 1.0-kilobase T beta gene transcript could be demonstrated at low levels in freshly isolated cells and at a much higher level in interleukin-2 (IL-2)-cultured cells. The transcript coding for the delta chain of the CD3 complex was also absent. These cells were cultured in IL-2 with or without the addition of the differentiation-inducing agents: retinoic acid, N,N-hexamethylene bisacetamide, and sodium butyrate. The cultured cells retained their NK activity except in culture with sodium butyrate at greater than or equal to 1 mmol/L. Expression of CD3 or other T cell surface markers by the NK cells was not observed in these cultures. Either CD2+, CD3- NK cells are derived from a non-T lineage, or they have diverged from the T cell lineage earlier than the stage of T gamma gene rearrangement and CD3 delta chain expression; they are refractory to many induction signals in undergoing further T cell differentiation.
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    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 3
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    Monoclonal antibodies against bovine tissue factor, which block interaction with factor VIIa (1985)
    American Society of Hematology
    Details
    Publication Date: 1985-07-01
    Description: Two monoclonal antibodies that recognize bovine tissue factor (coagulation factor III) have been obtained following the fusion of hyperimmune mouse spleen cells with NS-1 plasmacytoma cells. Both antibodies, TF1-E2 and TF1-F7, have gamma 1 heavy chains and lambda light chains. TF1-E2 and TF1-F7 have each been used to purify bovine tissue factor from a crude detergent extract of bovine brain by immunoaffinity chromatography. Both antibodies inhibit tissue factor procoagulant activity and block the association of factor VIIa with tissue factor. The association of TF1-F7 and tissue factor solubilized in Triton X-100 was measured under equilibrium conditions. The Kd for this antibody-antigen interaction was 2.1 +/- 0.2 nmol/L. TF1-E2 effectively competes with TF1-F7 for tissue factor binding, indicating that the monoclonal antibodies recognize overlapping sites on the protein. These antibodies will be useful reagents for large-scale purification and for structure-function studies of bovine tissue factor. In particular, since they appear to bind to the same region of the tissue factor molecule as factor VIIa, they will be useful as specific probes for studying the kinetics of tissue factor-initiated coagulation and for immunocytochemical localization of tissue factor in bovine cells.
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    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 4
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    An inhibitory monoclonal antibody against human tissue factor (1987)
    American Society of Hematology
    Details
    Publication Date: 1987-08-01
    Description: We obtained a hybridoma using immune spleen cells from a mouse injected with human brain tissue factor that had been purified on a factor VII- agarose affinity column. This monoclonal IgG1, HTF1–7B8, inhibits tissue factor procoagulant activity. The concentration of HTF1–7B8 producing half-maximal inhibition is influenced by the concentration of factor VIIa, suggesting that the antibody and enzyme compete for the cofactor. The antibody was successfully used to detect both human and bovine tissue factor on nitrocellulose dot blots, indicating that the epitope recognized by this antibody is conserved in both species. This antibody clearly reveals tissue factor on a Western blot. An HTF1–7B8 affinity column was used to purify tissue factor from both human brain and placenta. The electrophoretic mobilities in polyacrylamide gels in the presence of sodium dodecyl sulfate (SDS) and the amino acid compositions of the purified tissue factor from brain and placenta are indistinguishable, as are their specific procoagulant activities in reconstituted systems. This antibody will be useful for immunopurification and characterization of tissue factor structure and mechanism.
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    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 5
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    Monoclonal antibodies against bovine tissue factor, which block interaction with factor VIIa (1985)
    American Society of Hematology
    Details
    Publication Date: 1985-07-01
    Description: Two monoclonal antibodies that recognize bovine tissue factor (coagulation factor III) have been obtained following the fusion of hyperimmune mouse spleen cells with NS-1 plasmacytoma cells. Both antibodies, TF1-E2 and TF1-F7, have gamma 1 heavy chains and lambda light chains. TF1-E2 and TF1-F7 have each been used to purify bovine tissue factor from a crude detergent extract of bovine brain by immunoaffinity chromatography. Both antibodies inhibit tissue factor procoagulant activity and block the association of factor VIIa with tissue factor. The association of TF1-F7 and tissue factor solubilized in Triton X-100 was measured under equilibrium conditions. The Kd for this antibody-antigen interaction was 2.1 +/- 0.2 nmol/L. TF1-E2 effectively competes with TF1-F7 for tissue factor binding, indicating that the monoclonal antibodies recognize overlapping sites on the protein. These antibodies will be useful reagents for large-scale purification and for structure-function studies of bovine tissue factor. In particular, since they appear to bind to the same region of the tissue factor molecule as factor VIIa, they will be useful as specific probes for studying the kinetics of tissue factor-initiated coagulation and for immunocytochemical localization of tissue factor in bovine cells.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 6
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    An inhibitory monoclonal antibody against human tissue factor (1987)
    American Society of Hematology
    Details
    Publication Date: 1987-08-01
    Description: We obtained a hybridoma using immune spleen cells from a mouse injected with human brain tissue factor that had been purified on a factor VII- agarose affinity column. This monoclonal IgG1, HTF1–7B8, inhibits tissue factor procoagulant activity. The concentration of HTF1–7B8 producing half-maximal inhibition is influenced by the concentration of factor VIIa, suggesting that the antibody and enzyme compete for the cofactor. The antibody was successfully used to detect both human and bovine tissue factor on nitrocellulose dot blots, indicating that the epitope recognized by this antibody is conserved in both species. This antibody clearly reveals tissue factor on a Western blot. An HTF1–7B8 affinity column was used to purify tissue factor from both human brain and placenta. The electrophoretic mobilities in polyacrylamide gels in the presence of sodium dodecyl sulfate (SDS) and the amino acid compositions of the purified tissue factor from brain and placenta are indistinguishable, as are their specific procoagulant activities in reconstituted systems. This antibody will be useful for immunopurification and characterization of tissue factor structure and mechanism.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 7
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    Tumor necrosis factor-induced endothelial tissue factor is associated with subendothelial matrix vesicles but is not expressed on the apical surface (1992)
    American Society of Hematology
    Details
    Publication Date: 1992-08-15
    Description: Cultured endothelial cells can be induced by tumor necrosis factor/cachectin (TNF) and other cytokines to synthesize the procoagulant cofactor tissue factor (TF). Intact monolayers of TNF- treated endothelial cells showed only minimal TF activity. In contrast, after permeabilization of these monolayers with detergent (saponin, 0.02%), there was approximately 10- to 20-fold increase in TF-mediated, factor VIIa-dependent factor Xa formation. Extracellular matrix derived from TNF-treated endothelium, prepared after removing the cells by hypotonic lysis or ammonium hydroxide (0.1 N), also had similarly enhanced TF activity. Incubation with a blocking monoclonal antibody to TF inhibited the procoagulant activity of both TNF-stimulated endothelial cells, whether they were intact or permeabilized, and of their matrices. However, when the apical cell surface was pretreated with anti-TF antibody, washed, and then cells were lysed with water or permeabilized with saponin, similar augmentation of TF activity was still observed, suggesting the presence of a pool of TF to which the antibody did not initially gain access. Consistent with this concept, the presence of TF in the matrix of TNF-treated endothelial cells was shown by immunoblotting and morphologic studies; cultured endothelial monolayers and the native endothelium of aortic segments after exposure to TNF showed TF in extracellular matrix, associated with vesicles. In contrast, TF was virtually undetectable on the apical endothelial surface. Taken together, these findings suggest that endothelial TF can be present in a cryptic pool that only gains access to the blood after alteration in the integrity of the endothelial monolayer.
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  • 8
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    C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor (1993)
    American Society of Hematology
    Details
    Publication Date: 1993-07-15
    Description: The acute inflammatory response is frequently accompanied by serious thrombotic events. We show that C-reactive protein (CRP), an acute- phase reactant that markedly increases its serum concentration in response to inflammatory stimuli, induced monocytes to express tissue factor (TF), a potent procoagulant. Purified human CRP in concentrations commonly achieved in vivo during inflammation (10 to 100 micrograms/mL) induced a 75-fold increase in TF procoagulant activity (PCA) of human peripheral blood mononuclear cells (PBM), with a parallel increase in TF antigen levels. CRP-induced PCA was completely blocked by a monoclonal antibody against human TF but not by irrelevant murine IgG. Dot blot analysis showed a significant increase of TF mRNA after 4 hours of incubation with CRP, followed by a peak of PCA within 6 and 8 hours. Actinomycin D and cycloheximide blocked CRP-stimulated PCA, suggesting that de novo TF protein synthesis was required. Endotoxin (LPS) contamination of CRP was excluded as the mediator of TF synthesis because: (1) CRP was Limulus assay negative; (2) induction of TF PCA by CRP was not blocked by Polymyxin B, in contrast to LPS- induced PCA; (3) antihuman CRP IgG inhibited CRP-induced PCA, but not LPS-induced PCA; (4) CRP was able to stimulate TF production in LPS- pretreated PBM refractory to additional LPS stimulation; and, (5) unlike LPS, CRP was incapable of inducing TF in human umbilical vein endothelial cells. We suggest that CRP-mediated TF production in monocytes may contribute to the development of disseminated intravascular coagulation and thrombosis in inflammatory states.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 9
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    HLA associations with leukemia (1987)
    American Society of Hematology
    Details
    Publication Date: 1987-07-01
    Description: Frequencies of 35 HLA A, B, C, and DR antigens were determined in 1,834 leukemic Caucasoids to evaluate possible associations between HLA and leukemia. In comparison with the frequencies of HLA antigens in published controls, the frequency of Cw3 was significantly higher in patients with acute lymphoblastic leukemia (relative risk = 2.64, P less than 0.0002), acute myelogenous leukemia (relative risk = 1.92, P less than 0.0007), and chronic myelogenous leukemia (relative risk = 2.07, P less than 0.002; P values adjusted for multiple comparisons). The frequency of Cw4 was elevated in patients with acute lymphoblastic leukemia (relative risk = 2.01, P less than 0.0003), acute myelogenous leukemia (relative risk = 2.06, P less than 0.0002), and chronic myelogenous leukemia (relative risk = 2.14, P less than 0.0008). The frequency of Aw19 was significantly decreased in patients with acute myelogenous leukemia (relative risk = 0.68, P less than 0.01) and chronic myelogenous leukemia (relative risk = 0.59, P less than 0.005). None of the other 32 HLA antigens investigated had a statistically significant association with leukemia. The data suggest that Cw3 and Cw4 may be markers for leukemia susceptibility genes, while Aw19 may be a marker for decreased susceptibility to leukemia.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 10
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    Unknown
    C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor (1993)
    American Society of Hematology
    Details
    Publication Date: 1993-07-15
    Description: The acute inflammatory response is frequently accompanied by serious thrombotic events. We show that C-reactive protein (CRP), an acute- phase reactant that markedly increases its serum concentration in response to inflammatory stimuli, induced monocytes to express tissue factor (TF), a potent procoagulant. Purified human CRP in concentrations commonly achieved in vivo during inflammation (10 to 100 micrograms/mL) induced a 75-fold increase in TF procoagulant activity (PCA) of human peripheral blood mononuclear cells (PBM), with a parallel increase in TF antigen levels. CRP-induced PCA was completely blocked by a monoclonal antibody against human TF but not by irrelevant murine IgG. Dot blot analysis showed a significant increase of TF mRNA after 4 hours of incubation with CRP, followed by a peak of PCA within 6 and 8 hours. Actinomycin D and cycloheximide blocked CRP-stimulated PCA, suggesting that de novo TF protein synthesis was required. Endotoxin (LPS) contamination of CRP was excluded as the mediator of TF synthesis because: (1) CRP was Limulus assay negative; (2) induction of TF PCA by CRP was not blocked by Polymyxin B, in contrast to LPS- induced PCA; (3) antihuman CRP IgG inhibited CRP-induced PCA, but not LPS-induced PCA; (4) CRP was able to stimulate TF production in LPS- pretreated PBM refractory to additional LPS stimulation; and, (5) unlike LPS, CRP was incapable of inducing TF in human umbilical vein endothelial cells. We suggest that CRP-mediated TF production in monocytes may contribute to the development of disseminated intravascular coagulation and thrombosis in inflammatory states.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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