Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial cell activation may play a role in thrombotic complications of BMT such as hepatic veno-occlusive disease (VOD), right atrial line thrombosis and microangiopathic haemolysis. To assess this, von Willebrand factor antigen (vWF:ag) was measured in 72 patients (25 allografts, 46 autografts and one syngeneic) during the first 6 weeks post-transplant. There was a significant rise in vWF:ag in both allografts and autografts but a greater increase was seen in the allografts. The changes in vWF:ag did not correlate with changes in C reactive protein showing that this was not merely an acute phase response. vWF multimers were normal in a subgroup of uncomplicated transplants showing that there was no large scale endothelial cell disruption. Patients with VOD did not have changes in vWF:ag that were consistently different from uncomplicated controls. Three of four patients who developed line thrombosis had higher levels of vWF:ag compared with control groups; multimeric structure of the vWF was again normal. These results show that there is endothelial cell activation post-BMT and that this is greater in allografts compared with autografts, thus suggesting a possible mechanism for the higher incidence of VOD in this group. There were no useful predictive markers of VOD or thrombosis in individual patients.
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PMID:von Willebrand factor as a marker of endothelial cell activation following BMT. 149 Jan 99

The role of mixed hematopoietic chimerism in engraftment and relapse after allogeneic BMT remains unclear. To better evaluate post-transplant chimerism we used polymerase chain reaction (PCR) in vitro amplification of four single locus simple repetitive DNA sequences, all of which vary extensively in their repeat number among different individuals: variable number of tandem repeats D1S80, APOB and D17S5, and the tetranucleotide repeat F8VWF. We tested 13 cases of CML, four of multiple myeloma (MM), three of ANLL and one of B-CLL. In a sequential analysis protocol with the different loci, the donor could be distinguished from the recipient in 14 of 20 (70%) pairs with the first marker used (D1S80). When a donor of opposite sex was involved, karyotyping and Y chromosome-specific PCR were also used. With the use of the four markers, chimerism was identified in all the pairs. Mixed chimerism was present in 5 patients, and complete chimerism in 15. No patients relapsed. The application of PCR for documenting post-transplant chimerism has several advantages over Southern blotting: increased sensitivity, use of small amounts of sample, ease of preparation of DNA, elimination of restriction enzyme analysis and of radioisotopes, and speed.
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PMID:In vitro amplification of hypervariable DNA regions for the evaluation of chimerism after allogeneic BMT. 840 55

To investigate endothelial cell alterations in BMT recipients developing acute graft-versus-host disease (aGVHD) we determined levels of the endothelial cell markers von Willebrand factor (VWF) and thrombomodulin (TM) in 57 patients undergoing BMT. Before conditioning VWF and TM levels did not differ significantly between transplant recipients who later developed no or mild (grade I) aGVHD (group A, allogeneic n = 22, autologous n = 7; VWF 136.0 +/- 44.1%; TM 29.5 +/- 18.0 ng/ml), and those with moderate or severe (grade II or III) aGVHD (group B, n = 28; VWF 142.2 +/- 37.6%; TM 35.2 +/- 20.1 ng/ml). A first significant rise of both VWF and TM level was noted after conditioning (day 0) both in group A (VWF 197.0 +/- 113.3%; P < 0.001; TM 39.3 +/- 23.3 ng/ml; P < 0.01) as well as in group B (VWF 201.7 +/- 53.3%; P < 0.0001; TM 43.5 +/- 23.5 ng/ml; P < 0.05). Subgroup analysis of autografted patients revealed no significant increase after conditioning in these patients. At the time of engraftment and onset of aGVHD (day 21), when VWF and TM levels within the groups were significantly elevated as compared with baseline (day -8) levels, group B patients (62.7 +/- 38.5 ng/ml) had significantly higher (P < 0.01) TM levels than patients of group A (37.4 +/- 19.6 ng/ml). This significant elevation also persisted at the end of the investigational period (day 28; group B: 56.0 +/- 37.6 ng/ml; group A: 38.2 +/- 23.7 ng/ml; P < 0.01). An elevation of endothelial cell markers is found in the course of BMT, particularly after conditioning and at the time of engraftment. This increase is pronounced in patients with aGVHD suggesting not only epithelial cell but also endothelial cell injury during aGVHD.
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PMID:Endothelial cell markers in bone marrow transplant recipients with and without acute graft-versus-host disease. 915 65

Factors that enhance hypercoagulability following BMT may have a pathogenetic role in VOD. To investigate the relevance of hemostatic parameters for the development of VOD, we prospectively measured protein C, protein S, antithrombin III (AT III), von Willebrand factor, and factor VIII in 50 consecutive patients undergoing allogeneic BMT. Each parameter was determined before conditioning, on day 0 of BMT and weekly for 3 weeks, and patients were monitored prospectively for the occurrence of VOD. VOD occurred in 26 patients at median post-BMT day 8.5 (range, day -2 to 17). Thirteen patients had mild, 10 had moderate and three had severe VOD. No coagulation parameters were significantly different at the baseline or on day 0 of BMT between patients with no/mild VOD and moderate to severe VOD. On day 7 and thereafter, levels of protein C and AT III were significantly lower in patients with moderate to severe VOD when compared to patients with no/mild VOD. Levels of protein C and AT III decreased before the clinical onset of VOD in patients with moderate to severe VOD. Early post-BMT reduction of these parameters may indicate the development of moderate to severe VOD.
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PMID:Relevance of proteins C and S, antithrombin III, von Willebrand factor, and factor VIII for the development of hepatic veno-occlusive disease in patients undergoing allogeneic bone marrow transplantation: a prospective study. 982 16

Thrombotic thrombocytopenic purpura(TTP) is a multisystem disorders characterized by thrombocytopenia, microangiopathic hemolytic anemia associated with red cell fragmentation, and neurological and renal symptoms. Plasma of patients with TTP has been shown to contain unusually large von Willebrand factor(vWF) multimers that may cause platelet agglutination in vivo. Recently, a metalloprotease responsible for cleavage of vWF multimers has been isolated from normal human plasma and was found to be deficient in some patients with TTP. We examined the activity of the vWF-cleaving protease(vWF-CP), by modified Furlan's method, in plasma from patients with a familial TTP, 3 acquired TTP, 4 thrombotic microangiopathy(TMA) and 2 veno-occlusive disease(VOD) associated after allo-BMT. Diluted plasma samples of patients were incubated with protease-free vWF purified from normal human plasma, in the presence of urea and barium ions. The extent of vWF degradation was assayed by electrophoresis in SDS-agarose gels and immunoblotting. Activity of vWF-CP from 12 normal plasma have been shown as 77-180%(average 115%), whereas, no vWF-CP(below 5%) was observed in plasma from familial TTP, before and after plasma exchange, although FFP infusion therapy has been effective for this patient to recover thrombocytopenia. In 3 acquired TTP, 2 patients showed lack of vWF-CP activity in plasma, and inhibitors against vWF-CP have been elucidated by plasma cross-mixing test. After extensive plasma exchange and FFP infusion followed by corticosteroid therapy, normal vWF-CP was recovered in plasma from 2 acquired TTP patients. Among BMT patients, plasma from 4 BMT-TMA showed normal vWF-CP activities as 55-111%, whereas plasma from 2 BMT-VOD revealed low vWF-CP activity, as 24% and 37%, respectively. Thus, measurement of vWF-CP is crucial to predict differentiation of primary forms of TMA to establish the pathogenesis in varied endothelial dysfunction.
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PMID:[Measurement of plasma von Willebrand factor cleaving protease in patients with varied thrombotic microangiopathy]. 1288 37