Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes of prekallikrein in the cases with DIC were investigated, i.e., DIC cases including disseminated metastasis of gastric cancer, acute promyelocytic leukemia and endotoxin shock. Therefore, the trigger substances for this paper were the pathologic cells of the leukemia, the cultured well differentiated adenocarcinoma cells and endotoxin. (1) The lysates of the pathologic cells of the leukemia and the cultured cells showed prekallikrein activation. Endotoxin showed prekallikrein activation via factor XII. (2) Serine proteases (factor Xa, thrombin, plasmin and trypsin) activated prekallikrein in the plasma and the purified prekallikrein. (3) Antithrombin III, aprotinin and FOY inhibited prekallikrein activation. Antithrombin III was promoted by heparin in its inhibitory effect.
 ...
PMID:Changes of prekallikrein in the cases with disseminated intravascular coagulation syndrome. 16 Jan 91

Platelets from patients with myeloid leukaemia showed reduced aggregation with collagen or thrombin. These platelets also had a lower capacity to bind thrombin. This lower thrombin binding is due to a decrease in the total quantity of receptors available and not because of a change in the affinity. In the presence of the patients' plasma, the aggregation behaviour of normal platelets induced by thrombin as well as the clotting time of fibrinogen remained unchanged. The results suggest that the platelet dysfunction in myeloid leukaemia is partially due to a membrane defect involving the thrombin receptors which leads to an impaired induction of the initial stimulation.
 ...
PMID:Defective binding of thrombin to platelets in myeloid leukaemia. 27 56

In 22 patients with acute myeloid leukaemia (17 cases of myeloblastic leukaemia, 4 cases of myelomonocytic leukaemia and 1 case of undifferentiated-cell leukaemia) platelets were isolated from the plasma by the method of Nicholls and Hampton as modified by Levy-Toledano by centrifugation in albumin gradient. The aim of platelet isolation was their "concentration" in cases of thrombocytopenia to values making possible aggregation tests, and platelet separation from the influence of plasma factors. Then aggregation of isolated platelets caused by ADP was studied. In 16 out of 22 patients a fall of aggregation was observed, with the mean values of aggregation rate and intensity were significantly lower. Parallelly done determinations of aggregating activity released from the platelets by thrombin showed lower values as compared with platelets from healthy subjects. In might be thought, in this connection, that the demonstrated reduction of isolated platelets is associated with a diminution of the nucleotide pool or disturbances of the platelet release reaction. The disturbances of the platelet release reaction. The disturbances of aggregation of isolated platelets and reduction of the aggregating activity were most pronounced in acute myelomonocytic leukaemia.
 ...
PMID:[Platelet function in acute myeloid leukemia. II. Aggregation of isolated platelets]. 28 Oct 86

Platelets from a patient with eosinophilic leukaemia were not aggregated by ristocetin. The defect was not corrected by normal human plasma and was due to a platelet abnormality. The patient's platelets also showed a diminished sensitivity to aggregation by bovine factor VIIIVWF. The defect was not associated with a prolonged bleeding time. No abnormalities were detected in ADP, collagen or thrombin-induced platelet aggregation. Biochemical studies showed that the platelets were deficient in sialic acid. This deficiency was associated with a reduced staining for glycoprotein I following SDS-polyacrylamide gel electrophoresis. The results suggest an acquired platelet surface abnormality.
 ...
PMID:A platelet defect in a patient with eosinophilic leukaemia: absent ristocetin-induced platelet aggregation associated with a reduced platelet sialic acid content. 45 58

A quantitative study of various aspects of platelet function was carried out in eight patients with typical hairy-cell leukaemia (HCL). In at least two patients platelet aggregation was convincingly reduced to more than one aggregating agent (ADP, adrenaline, collagen, thrombin, and ristocetin). Granular storage capacity for {(14)C} 5-HT was reduced in five of the six patients tested. The two patients with definitely abnormal aggregation had the greatest reduction in granular storage pool and the longest bleeding times of those tested but, like the other patients, they did not have a clinical haemostatic defect. It was concluded that a granular storage pool defect (SPD) was at least partly responsible for aggregation abnormalities in HCL since the platelet release reaction in response to thrombin appeared to be normal. All our patients ran a chronic course uncomplicated by any of the factors known to predispose to a platelet SPD acquired in the circulation. Although in the one patient tested before and after splenectomy there was some improvement in platelet aggregation after operation, there was no clear general relationship between defective platelet function and either previous splenectomy or platelet count. Since a direct involvement of the megakaryocytic series in the underlying cell proliferation of HCL seems unlikely, it is concluded that the platelet defect can most reasonably be attributed to the production of abnormal platelets as a result of marrow fibrosis and/or infiltration by hairy cells.
 ...
PMID:Platelet function in hairy-cell leukaemia. 51 41

Immobilized asparaginase was prepared by embedding asparaginase (which is effective for remission in children with leukemia) into fibrin polymer formed by fibrinogen-fibrin conversion in the presence of thrombin. The immobilized asparaginase film did not dissolve in 6 mol/1 urea, suggesting that blood coagulation factor XIII participates in the cross-linking between fibrins and between fibrin and asparaginase.
 ...
PMID:Immobilized L-asparginase embedded in fibrin polymer. 109 44

A consumption coagulopathy syndrome has frequently been reported in association with some cases of acute nonlymphoblastic leukemia (ANLL) and mainly in acute promyelocytic leukemia (M3). Eighteen cases of ANLL have been studied on admission, before chemotherapy was started. Levels of antithrombin III (AT-III), protein C (PC), protein S (PS), thrombin-antithrombin complex (T-AT-III), tissue plasminogen activator, plasminogen (Pg), alpha-2-antiplasmin (alpha-2-AP), D-dimer (DD) and fibrinogen (Fg) were determined. The results showed normal levels of AT-III and PS, decreased levels of PC, alpha-2-AP, Pg and Fg in some cases, and an elevation of DD and T-AT III complex in almost all patients. There was a continuous evolution of data from M1 cases in which only slight alterations were seen up to M3 cases where all those pathologic data were observed.
 ...
PMID:A continuous spectrum of hypercoagulability exists in acute nonlymphoblastic leukemia. 128 98

To study thrombin's receptor-mediated effects on vascular cells, we cloned and characterized a cDNA encoding a rat smooth muscle cell thrombin receptor. A rat aortic smooth muscle (RASM) cell cDNA library was screened with a 500-base pair (bp) sequence from the human thrombin receptor, obtained by polymerase chain reaction (PCR) amplification of cDNA synthesized from human erythropoietic leukemia (HEL) cell mRNA with PCR primers based on the published human thrombin receptor sequence. Clone pRTHR17 contains a 3418-bp insert that includes 50 bp of the 5'-untranslated region and the entire coding and 3'-untranslated regions of the RASM cell thrombin receptor. The sequence of pRTHR17 is 85% similar, at the nucleotide level, and 78% similar, at the deduced amino acid level, to the human thrombin receptor. Although the putative thrombin cleavage and binding sites are present, there are significant differences between the rat and human receptors in their amino-terminal sequences. Detectable signals (consisting of a single band of 3.45 kb) are present by Northern analysis of mRNA from RASM cells, and rat lung, kidney, and testes, but not in aorta or other tissues probed. The results of Southern analysis of rat genomic DNA are consistent with the existence of a single copy of the gene encoding this receptor. The steady state thrombin receptor mRNA level is low in cultured growth-arrested RASM cells and not detectable in rat aorta. To determine whether regulation of the RASM cell thrombin receptor occurs under growth-stimulating conditions, growth-arrested RASM cells were treated with basic fibroblast growth factor (bFGF, recently proposed to be a major mitogen controlling vascular smooth muscle cell growth following injury (Lindner, V., and Reidy, M. A. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 3739-3743)). There was a significant increase in thrombin receptor mRNA following the addition of bFGF. These data demonstrate that: 1) mRNA for a thrombin receptor similar to that reported from human megakaryocyte and hamster fibroblast cell lines is present in proliferating primary culture rat smooth muscle cells, 2) the most significant sequence differences are present in the amino-terminal tail of the thrombin receptor, and 3) the mRNA level for this receptor is regulated under growth-stimulating conditions in vitro.
 ...
PMID:Molecular cloning of the rat vascular smooth muscle thrombin receptor. Evidence for in vitro regulation by basic fibroblast growth factor. 132 17

The precursor of matrix metalloproteinase 9 (proMMP-9), also known as '92 kDa progelatinase/type IV procollagenase', was purified from the conditioned medium of U937 monocytic leukaemia and HT1080 fibrosarcoma cell lines stimulated with phorbol 12-myristate 13-acetate. ProMMP-9 in these culture media is non-covalently complexed with the 29 kDa tissue inhibitor of metalloproteinases (TIMP), but free proMMP-9 was separated from the TIMP-proMMP-9 complex by chromatography on Green A Dyematrex gel. The final product was homogeneous on SDS/PAGE, with a molecular mass of 88 kDa without reduction and 92 kDa with reduction. Treatment of proMMP-9 with 4-aminophenylmercuric acetate converted the 88 kDa precursor into 80 kDa and 68 kDa forms. Gelatin-containing zymographic analysis showed zones of lysis associated with all three species. However, only the 68 kDa species was shown to be catalytically active by its ability to bind to alpha 2-macroglobulin. In the presence of an equimolar amount of TIMP, only the 80 kDa species was generated by treatment with 4-aminophenylmercuric acetate, but no enzyme activity was detected. This indicates that TIMP binds to the 80 kDa intermediate and inhibits the generation of the active 68 kDa species. Eight endopeptidases (trypsin, chymotrypsin, plasmin, plasma kallikrein, thrombin, cathepsin G, neutrophil elastase and thermolysin) were tested for their ability to activate proMMP-9. Of them, trypsin was the most effective activator of proMMP-9. Only partial activation (10-30%) was observed with plasmin, cathepsin G and chymotrypsin. The active forms generated by trypsin were identified as 80 kDa, 74 kDa and 66 kDa by their abilities to bind to alpha 2-macroglobulin. In the presence of an equimolar amount of TIMP, proMMP-9 was also converted into the same molecular-mass species by trypsin, but they were not proteolytically active. This suggests activated MMP-9 is inhibited by TIMP. Activated MMP-9 digested gelatin, type-V collagen, reduced carboxymethylated transferrin and, to a lesser extent, type-IV collagen and laminin A chain. The specific activity against gelatin was estimated to be 15,000 units/mg (1 unit = 1 microgram of gelatin degraded/min at 37 degrees C) by titration with alpha 2-macroglobulin. Comparative studies on digestion of gelatin and collagen types IV and V by MMP-9 and MMP-2 indicated that both enzymes degrade these substrates into similar fragments. However, the susceptibilities of laminin, fibronectin and reduced carboxymethylated transferrin to these two MMPs were sufficiently different to indicate differences in substrate specificities between these two closely related proteinases.
 ...
PMID:Purification and characterization of matrix metalloproteinase 9 from U937 monocytic leukaemia and HT1080 fibrosarcoma cells. 137 48

Plasma concentration of thrombin-antithrombin III complex (TAT), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), PAI-2, D-dimer complex and urokinase-plasminogen activator (u-PA) activity were studied in 30 patients with acute nonlymphoblastic leukemia (ANLL), before and during antileukemic therapy. Fifteen patients showed signs of disseminated intravascular coagulation (DIC), 10 of them classified as M3, 2 as M2 and 3 as M5 subtypes. The initial levels of TAT complex were elevated in all ANLL patients. This increase was more pronounced in patients with DIC (p less than 0.05). TAT increased significantly during the treatment period in all cases. u-PA and PAI-1 levels were elevated but there were no statistically significant differences between patients with and without DIC. PAI-2 levels were below the limit of detection in controls and in patients. However, the initially elevated D-dimer complex levels were significantly higher in DIC cases (p less than 0.01) and they increased during the treatment period. A significant and positive correlation between D-dimer and TAT complex values was found in DIC patients (r = 0.68, p less than 0.001). The high TAT complex and D-dimer levels further increased during chemotherapy treatment strongly suggest a hypercoagulable state with secondary activation of fibrinolysis not severe enough to manifest itself as clinically evident DIC in the majority of cases.
 ...
PMID:Increase in the D-dimer levels during treatment in patients with acute myelogenous leukemia. 142 55


1 2 3 4 5 6 7 8 9 10 Next >>