Cabbage seed protease inhibitor: a slow, tight-binding inhibitor of trypsin with activity toward thrombin, activated Stuart factor (factor Xa), activated Hageman factor (factor XIIa), and plasmin.


:An inhibitor of procoagulant and fibrinolytic enzymes was derived from cabbage seeds by a procedure using acetone precipitation, ion-exchange chromatography, and gel filtration. The cabbage seed inhibitor was a 10-Kd monomeric protein with intrachain disulfide bonds. This preparation prevented clot formation in whole blood and blocked the ability of thrombin to induce clot formation in plasma and to induce platelet aggregation. A number of proteases were inhibited, as demonstrated by using purified enzymes in amidolytic assays. Tight-binding inhibition was observed for activated Stuart factor (factor Xa) and plasmin. Inhibition of thrombin and activated Hageman factor (factor XIIa) was observed with a molar excess of inhibitor. No inhibition was detected for activated plasma thromboplastin antecedent (factor XIa), plasma kallikrein, or C1 esterase. Reaction progress curves for trypsin indicated slow, tight-binding inhibition, with an apparent inhibition constant in the nanomolar range or less. The electrophoretic mobility of trypsin was altered by the inhibitor in nondenaturing polyacrylamide gel electrophoresis (PAGE) but not in sodium dodecyl sulfate (SDS)-PAGE, indicating noncovalent bonding. Only partial reversal of trypsin inhibition could be demonstrated by washing the inhibitor from enzyme immobilized on solid beads. A dot-blot technique with cabbage seed inhibitor was capable of detecting 10 ng nitrocellulose-bound trypsin. The dot-blot technique also appeared capable of detecting plasmin. These findings demonstrated the potential utility of this inhibitor as a probe for detection of tightly bound proteases. In summary, cabbage seed extracts contain an inhibitor with activity toward a broad range of proteases important to hemostasis. To our knowledge, this agent represents the first inhibitor isolated from a plant source that inhibits thrombin.






Carter TH,Everson BA,Ratnoff OD


Has Abstract


1990-01-01 00:00:00














  • Constitutive expression of GATA-1, EPOR, alpha-globin, and gamma-globin genes in myeloid clonogenic cells from juvenile chronic myelocytic leukemia.

    abstract::Juvenile chronic myelocytic leukemia (JCML) is a rare disorder of early childhood. Characteristic of JCML are the progressive appearance of high levels of fetal hemoglobin (HbF), reflecting a true reversion to a fetal type of erythropoiesis, and the presence of colony-forming cells able to grow in vitro spontaneously ...


    pub_type: 杂志文章


    authors: Privitera E,Schirò R,Longoni D,Ronchi A,Rambaldi A,Bernasconi S,Ottolenghi S,Masera G,Biondi A

    更新日期:1995-07-01 00:00:00

  • Warfarin-induced venous limb ischemia/gangrene complicating cancer: a novel and clinically distinct syndrome.

    abstract::Venous limb gangrene (VLG) can occur in cancer patients, but the clinical picture and pathogenesis remain uncertain. We identified 10 patients with metastatic cancer (7 pathologically proven) who developed severe venous limb ischemia (phlegmasia/VLG) after initiating treatment of deep-vein thrombosis (DVT); in 8 patie...


    pub_type: 杂志文章


    authors: Warkentin TE,Cook RJ,Sarode R,Sloane DA,Crowther MA

    更新日期:2015-07-23 00:00:00

  • Plasma crosslinked fibrin polymers: quantitation based on tissue plasminogen activator conversion to D-dimer and measurement in normal and patients with acute thrombotic disorders.

    abstract::Plasma crosslinked fibrin polymers (XLFP) are formed as a result of in vivo hemostatic activation and are elevated in thrombotic disease. We have investigated the plasmic degradation of plasma XLFP in vitro to provide information regarding the pattern of crosslinking and the composition of degradation products. Plasma...


    pub_type: 杂志文章


    authors: Kornberg A,Francis CW,Marder VJ

    更新日期:1992-08-01 00:00:00

  • Allo-HLA-reactive T cells inducing graft-versus-host disease are single peptide specific.

    abstract::T-cell alloreactivity directed against non-self-HLA molecules has been assumed to be less peptide specific than conventional T-cell reactivity. A large variation in degree of peptide specificity has previously been reported, including single peptide specificity, polyspecificity, and peptide degeneracy. Peptide polyspe...


    pub_type: 杂志文章


    authors: Amir AL,van der Steen DM,Hagedoorn RS,Kester MG,van Bergen CA,Drijfhout JW,de Ru AH,Falkenburg JH,van Veelen PA,Heemskerk MH

    更新日期:2011-12-22 00:00:00

  • Proteolytic antibodies activate factor IX in patients with acquired hemophilia.

    abstract::Acquired hemophilia is a rare bleeding disorder characterized by the spontaneous occurrence of inhibitory antibodies against endogenous factor VIII (FVIII). IgG from some patients with acquired hemophilia hydrolyze FVIII. Because of the complex etiology of the disease, no clinical parameter, including the presence of ...


    pub_type: 临床试验,杂志文章


    authors: Wootla B,Christophe OD,Mahendra A,Dimitrov JD,Repessé Y,Ollivier V,Friboulet A,Borel-Derlon A,Levesque H,Borg JY,Andre S,Bayry J,Calvez T,Kaveri SV,Lacroix-Desmazes S

    更新日期:2011-02-17 00:00:00

  • Distinct apoptotic responses imparted by c-myc and max.

    abstract::The c-myc oncoprotein accelerates programmed cell death (apoptosis) after growth factor deprivation or pharmacological insult in many cell lines. We have shown that max, the obligate c-myc heterodimeric partner protein, also promotes apoptosis after serum withdrawal in NIH3T3 fibroblasts or cytokine deprivation in int...


    pub_type: 杂志文章


    authors: Nesbit CE,Fan S,Zhang H,Prochownik EV

    更新日期:1998-08-01 00:00:00

  • VH gene rearrangement events can modify the immunoglobulin heavy chain during progression of B-lineage acute lymphoblastic leukemia.

    abstract::The presence of multiple VHDJH joinings in upwards of 30% of acute lymphoblastic leukemias (ALL) suggests a relative instability of the rearranged immunoglobulin heavy chain (IgH) gene, but the mechanisms involved are not completely understood. An investigation of the structure of the VHDJH joinings using complementar...


    pub_type: 杂志文章


    authors: Wasserman R,Yamada M,Ito Y,Finger LR,Reichard BA,Shane S,Lange B,Rovera G

    更新日期:1992-01-01 00:00:00

  • The t(12;21) of acute lymphoblastic leukemia results in a tel-AML1 gene fusion.

    abstract::Analysis of a growing number of chromosomal translocations in human tumors have shown that they frequently result in gene fusions encoding chimeric proteins. We have characterized the recurrent t(12;21)(p12;q22) translocation present in human B-lineage acute leukemias. This translocation fused two genes, tel and AML1,...


    pub_type: 杂志文章


    authors: Romana SP,Mauchauffé M,Le Coniat M,Chumakov I,Le Paslier D,Berger R,Bernard OA

    更新日期:1995-06-15 00:00:00

  • Large granular lymphocytes in human peripheral blood: ultrastructural and cytochemical characterization of the granules.

    abstract::Large granular lymphocytes (LGL) are defined as nonadherent mononuclear cells with cytoplasmic azurophilic granules, avid receptors for the Fc portion of IgG, and cytotoxic functions (NK or ADCC activities). In the present study, the granules of LGL isolated from human peripheral blood have been analyzed by enzyme cyt...


    pub_type: 杂志文章


    authors: Grossi CE,Cadoni A,Zicca A,Leprini A,Ferrarini M

    更新日期:1982-02-01 00:00:00

  • Immunophenotypic analysis of B cells in PNH: insights into the generation of circulating naive and memory B cells.

    abstract::Peripheral blood B cells in patients with paroxysmal nocturnal hemoglobinuria (PNH) comprise variable mixtures of normal B cells produced before the onset of disease and glycosylphosphatidylinositol (GPI)-deficient B cells derived from the PNH hematopoietic stem cell. In a detailed phenotypic analysis of 29 patients w...


    pub_type: 杂志文章


    authors: Richards SJ,Morgan GJ,Hillmen P

    更新日期:2000-11-15 00:00:00

  • STAT3 and MAPK signaling maintain overexpression of heat shock proteins 90alpha and beta in multiple myeloma cells, which critically contribute to tumor-cell survival.

    abstract::The combined blockade of the IL-6R/STAT3 and the MAPK signaling pathways has been shown to inhibit bone marrow microenvironment (BMM)-mediated survival of multiple myeloma (MM) cells. Here, we identify the molecular chaperones heat shock proteins (Hsp) 90alpha and beta as target genes of both pathways. The siRNA-media...


    pub_type: 杂志文章


    authors: Chatterjee M,Jain S,Stühmer T,Andrulis M,Ungethüm U,Kuban RJ,Lorentz H,Bommert K,Topp M,Krämer D,Müller-Hermelink HK,Einsele H,Greiner A,Bargou RC

    更新日期:2007-01-15 00:00:00

  • How I perform hematopoietic stem cell transplantation on patients with a history of invasive fungal disease.

    abstract::Hematopoietic transplantation is the preferred treatment for many patients with hematologic malignancies. Some patients may develop invasive fungal diseases (IFDs) during initial chemotherapy, which need to be considered when assessing patients for transplantation and treatment posttransplantation. Given the associate...


    pub_type: 杂志文章


    authors: Puerta-Alcalde P,Champlin RE,Kontoyiannis DP

    更新日期:2020-12-10 00:00:00

  • The hydroxyurea-induced small GTP-binding protein SAR modulates gamma-globin gene expression in human erythroid cells.

    abstract::Hydroxyurea (HU), a drug effective in the treatment of sickle cell disease, is thought to indirectly promote fetal hemoglobin (Hb F) production by perturbing the maturation of erythroid precursors. The molecular mechanisms involved in HU-mediated regulation of gamma-globin expression are currently unclear. We identifi...


    pub_type: 杂志文章


    authors: Tang DC,Zhu J,Liu W,Chin K,Sun J,Chen L,Hanover JA,Rodgers GP

    更新日期:2005-11-01 00:00:00

  • Diferric transferrin regulates transferrin receptor 2 protein stability.

    abstract::Transferrin receptor 2 (TfR2) is a type 2 transmembrane protein expressed in hepatocytes that binds iron-bound transferrin (Tf). Mutations in TfR2 cause one form of hereditary hemochromatosis, a disease in which excessive absorption of dietary iron can lead to liver cirrhosis, diabetes, arthritis, and heart failure. T...


    pub_type: 杂志文章


    authors: Johnson MB,Enns CA

    更新日期:2004-12-15 00:00:00

  • Not fibrin(ogen), but fibrinogen or fibrin.

    abstract::In this issue of Blood, Prasad et al describe a mouse model with a mutation in the Aα chain of fibrinogen such that no fibrin polymer is formed in vivo, allowing for the first time the differentiation of the role of fibrinogen vs fibrin oligomer or polymer in antimicrobial host defense and in hemostasis/thrombosis. ...


    pub_type: 评论,杂志文章


    authors: Litvinov RI,Weisel JW

    更新日期:2015-10-22 00:00:00

  • Regulation of Toll-like receptor-mediated inflammatory response by complement in vivo.

    abstract::Toll-like receptors (TLRs) and complement are 2 components of innate immunity that are critical for first-line host defense and elicitation of adaptive immune responses. Many pathogen-associated molecular patterns activate both TLR and complement, but whether and how these 2 systems, when coactivated in vivo, interact...


    pub_type: 杂志文章


    authors: Zhang X,Kimura Y,Fang C,Zhou L,Sfyroera G,Lambris JD,Wetsel RA,Miwa T,Song WC

    更新日期:2007-07-01 00:00:00

  • The kringle stabilizes urokinase binding to the urokinase receptor.

    abstract::The structural basis of the interaction between single-chain urokinase-type plasminogen activator (scuPA) and its receptor (uPAR) is incompletely defined. Several observations indicated the kringle facilitates the binding of uPA to uPAR. A scuPA variant lacking the kringle (Delta K-scuPA) bound to soluble uPAR (suPAR)...


    pub_type: 杂志文章


    authors: Bdeir K,Kuo A,Sachais BS,Rux AH,Bdeir Y,Mazar A,Higazi AA,Cines DB

    更新日期:2003-11-15 00:00:00

  • Correlation between antiphospholipid antibodies that recognize domain I of beta2-glycoprotein I and a reduction in the anticoagulant activity of annexin A5.

    abstract::The paradoxical correlation between thrombosis and the lupus anticoagulant (LAC) effect is an enigmatic feature of the antiphospholipid (aPL) syndrome. The Dutch authors previously reported that thrombosis-related anti-beta2-glycoprotein I (beta2GPI) antibodies recognize domain I and cause LAC. The American authors re...


    pub_type: 杂志文章


    authors: de Laat B,Wu XX,van Lummel M,Derksen RH,de Groot PG,Rand JH

    更新日期:2007-02-15 00:00:00

  • Autoantibodies against the fibrinolytic receptor, annexin 2, in antiphospholipid syndrome.

    abstract::The association of thrombosis and gestational morbidity with antiphospholipid antibodies is termed antiphospholipid syndrome (APS). Annexin 2 (A2) is a profibrinolytic endothelial cell surface receptor that binds plasminogen, its tissue activator (tPA), and beta(2)-glycoprotein I (beta2GPI), the main antigen for antip...


    pub_type: 杂志文章


    authors: Cesarman-Maus G,Ríos-Luna NP,Deora AB,Huang B,Villa R,Cravioto Mdel C,Alarcón-Segovia D,Sánchez-Guerrero J,Hajjar KA

    更新日期:2006-06-01 00:00:00

  • Identification of cord blood dendritic cells as an immature CD11c- population.

    abstract::Dendritic cells (DC) are the main stimulators of primary T-cell responses and, thus, probably play a role in the immune reactions after stem cell transplantation. Very little is known about DC in cord blood (CB) and about their potential involvement in the low incidence and severity of acute graft-versus-host disease ...


    pub_type: 杂志文章


    authors: Sorg RV,Kögler G,Wernet P

    更新日期:1999-04-01 00:00:00

  • Recipient T lymphocytes modulate the severity of antibody-mediated transfusion-related acute lung injury.

    abstract::Transfusion-related acute lung injury (TRALI) is a serious complication of transfusion and has been ranked as one of the leading causes of transfusion-related fatalities. Nonetheless, many details of the immunopathogenesis of TRALI, particularly with respect to recipient factors are unknown. We used a murine model of ...


    pub_type: 杂志文章


    authors: Fung YL,Kim M,Tabuchi A,Aslam R,Speck ER,Chow L,Kuebler WM,Freedman J,Semple JW

    更新日期:2010-10-21 00:00:00

  • VEGF(165) promotes survival of leukemic cells by Hsp90-mediated induction of Bcl-2 expression and apoptosis inhibition.

    abstract::Similar to endothelial cells (ECs), vascular endothelial growth factor (VEGF) induces Bcl-2 expression on VEGF receptor-positive (VEGFR(+)) primary leukemias and cell lines, promoting survival. We investigated the molecular pathways activated by VEGF on such leukemias, by performing a gene expression analysis of VEGF-...


    pub_type: 杂志文章


    authors: Dias S,Shmelkov SV,Lam G,Rafii S

    更新日期:2002-04-01 00:00:00

  • Proteomics-based discovery of a novel, structurally unique, and developmentally regulated plasminogen receptor, Plg-RKT, a major regulator of cell surface plasminogen activation.

    abstract::Activation of plasminogen, the zymogen of the primary thrombolytic enzyme, plasmin, is markedly promoted when plasminogen is bound to cell surfaces, arming cells with the broad spectrum proteolytic activity of plasmin. In addition to its role in thrombolysis, cell surface plasmin facilitates a wide array of physiologi...


    pub_type: 杂志文章


    authors: Andronicos NM,Chen EI,Baik N,Bai H,Parmer CM,Kiosses WB,Kamps MP,Yates JR 3rd,Parmer RJ,Miles LA

    更新日期:2010-02-18 00:00:00

  • Concomitant inactivation of Rb and E2f8 in hematopoietic stem cells synergizes to induce severe anemia.

    abstract::The retinoblastoma (Rb) tumor suppressor plays important roles in regulating hematopoiesis, particularly erythropoiesis. In an effort to understand whether Rb function can be mediated by E2F transcription factors in a BM-derived hematopoietic system in mice, we uncovered a functional synergy between Rb and E2F8 to pro...


    pub_type: 杂志文章


    authors: Hu T,Ghazaryan S,Sy C,Wiedmeyer C,Chang V,Wu L

    更新日期:2012-05-10 00:00:00

  • Endotoxin-induced changes in human platelet membranes: morphologic evidence.

    abstract::Interaction between human platelets and bacterial endotoxin was studied in vitro with transmission and scanning electron microscopy. Washed human platelets, whose aggregation was blocked with apyrase, were incubated in a plasma-free medium containing crude endotoxin that had previously been complexed with copper. Thir...


    pub_type: 杂志文章


    authors: Ausprunk DH,Das J

    更新日期:1978-03-01 00:00:00

  • SDX-308, a nonsteroidal anti-inflammatory agent, inhibits NF-kappaB activity, resulting in strong inhibition of osteoclast formation/activity and multiple myeloma cell growth.

    abstract::Multiple myeloma is characterized by increased osteoclast activity that results in bone destruction and lytic lesions. With the prolonged overall patient survival achieved by new treatment modalities, additional drugs are required to inhibit bone destruction. We focused on a novel and more potent structural analog of ...


    pub_type: 杂志文章


    authors: Feng R,Anderson G,Xiao G,Elliott G,Leoni L,Mapara MY,Roodman GD,Lentzsch S

    更新日期:2007-03-01 00:00:00

  • MALT1 and the API2-MALT1 fusion act between CD40 and IKK and confer NF-kappa B-dependent proliferative advantage and resistance against FAS-induced cell death in B cells.

    abstract::The most frequently recurring translocations in mucosa-associated lymphoid tissue (MALT) B-cell non-Hodgkin lymphoma, t(11;18)(q21;q21) and t(14;18)(q32; q21), lead to formation of an API2-MALT1 fusion or IgH-mediated MALT1 overexpression. Various approaches have implicated these proteins in nuclear factor kappaB (NF-...


    pub_type: 杂志文章


    authors: Ho L,Davis RE,Conne B,Chappuis R,Berczy M,Mhawech P,Staudt LM,Schwaller J

    更新日期:2005-04-01 00:00:00

  • Thrombopoietin signal transduction in purified murine megakaryocytes.

    abstract::Thrombopoietin (TPO) is a recently cloned cytokine that binds to its receptor, Mpl, and promotes hematopoietic expansion and maturation, primarily of the megakaryocyte lineage. The signaling pathways responsible for these events are thought to involve the Janus family of nonreceptor tyrosine kinases (JAKs) and the sig...


    pub_type: 杂志文章


    authors: Drachman JG,Sabath DF,Fox NE,Kaushansky K

    更新日期:1997-01-15 00:00:00

  • Therapeutic targeting of HES1 transcriptional programs in T-ALL.

    abstract::Oncogenic activation of NOTCH1 signaling plays a central role in the pathogenesis of T-cell acute lymphoblastic leukemia, with mutations on this signaling pathway affecting more than 60% of patients at diagnosis. However, the transcriptional regulatory circuitries driving T-cell transformation downstream of NOTCH1 rem...


    pub_type: 杂志文章


    authors: Schnell SA,Ambesi-Impiombato A,Sanchez-Martin M,Belver L,Xu L,Qin Y,Kageyama R,Ferrando AA

    更新日期:2015-04-30 00:00:00

  • Physiologic and aberrant regulation of memory T-cell trafficking by the costimulatory molecule CD28.

    abstract::Productive T-cell immunity requires both the activation and the migration of specific T cells to the antigenic tissue. The costimulatory molecule CD28 plays an essential role in the initiation of T-cell-mediated immunity. We investigated the possibility that CD28 may also regulate migration of primed T cells to target...


    pub_type: 杂志文章


    authors: Mirenda V,Jarmin SJ,David R,Dyson J,Scott D,Gu Y,Lechler RI,Okkenhaug K,Marelli-Berg FM

    更新日期:2007-04-01 00:00:00