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991.
Phospholipase abolishes the effect of stimulated platelets on the thrombin activation of factor VIII
Factor VIII functions as a cofactor in the intrinsic coagulation pathway and must first be activated to function optimally in this capacity. Low concentrations of thrombin activate factor VIII, and the presence of stimulated platelets is known to enhance the activation of factor VIII complexed to von Willebrand factor. The current studies show that platelets stimulated by thrombin, collagen, or calcium ionophore will increase the activation of isolated factor VIII by thrombin. Ongoing platelet release is not necessary for the enhanced factor VIII activation, nor is platelet von Willebrand factor or platelet membrane glycoproteins Ib or IIb/IIIa. Platelet membrane phospholipids, on the other hand, are important for the enhanced activation of factor VIII by thrombin because the effect of stimulated platelets is abolished by incubation of the stimulated platelets with phospholipases. These results suggest that the enhanced activation of factor VIII by thrombin in the presence of stimulated platelets may be mediated by factor VIII binding to platelet phospholipid or to a receptor whose functional integrity is dependent on surrounding membrane phospholipid. 相似文献
992.
Allogeneic bone marrow transplantation for acute nonlymphocytic leukemia in first remission 总被引:1,自引:0,他引:1
McGlave PB; Haake RJ; Bostrom BC; Brunning R; Hurd DD; Kim TH; Nesbit ME; Vercellotti GM; Weisdorf D; Woods WG 《Blood》1988,72(5):1512-1517
Seventy-three patients with acute nonlymphocytic leukemia in first complete remission (CR) have received allogeneic bone marrow transplantation (BMT) with non-T-lymphocyte-depleted marrow obtained from matched sibling donors. The first 36 patients received a preparative regimen consisting of cyclophosphamide, 60 mg/kg/d (days -6 and -5), and 750 cGy single-dose total-body irradiation (TBI) (day -1). Subsequently, 37 patients received cyclophosphamide 60 mg/kg/d (days -6 and -5), and 165 cGy fractionated TBI administered twice daily for a total dose of 1,320 cGy (days -4, -3, -2, and -1). Survivors have been followed from 9 to 124 months (median, 40 months). The 61% (95% confidence interval [CI], 45% to 77%) projected disease-free survival (DFS) of 41 children less than 18 years old does not differ significantly from the 62% (95% CI, 49% to 73%) projected DFS of 32 adults at 84 months (P = .89). Similarly, the 15% (95% CI, 1% to 29%) projected relapse rate seen in children does not differ from the 9% (95% CI, 0% to 21%) seen in adults (P = .69). Multivariate Cox regression analysis of presenting features demonstrates that a presenting WBC count greater than 20,000/m3 is associated with decreased DFS (P = .01). When compared with other French-American- British (FAB) subtypes, presentation with FAB M4 or M5 morphology is significantly associated with relapse in multivariate analysis (P = .014). Other presenting features such as preparation with single-dose or fractionated TBI, interval from diagnosis to CR or CR to BMT, donor or recipient sex, and donor or recipient cytomegalovirus serology do not correlate independently with either DFS or relapse. When included in the stepwise multivariate analysis of presenting patient features, two posttransplant events, development of grades 2 to 4 acute graft-v- host disease (GVHD) (P less than .03) and development of interstitial pneumonitis (P less than .001), also correlate independently with poor DFS. Allogeneic BMT provides equivalent, prolonged DFS in both children and young adults when performed in first CR and should be considered the therapy of choice for all first CR patients under 45 years of age with a suitable donor. Continued efforts to prevent and treat acute GVHD and pneumonitis as well as efforts designed to prevent relapse in patients presenting with FAB M4 and M5 morphology should further improve outcome. 相似文献
993.
Structural integrity of the glycoprotein IIb and IIIa genes in Glanzmann thrombasthenia patients from Israel 总被引:3,自引:0,他引:3
Russell ME; Seligsohn U; Coller BS; Ginsberg MH; Skoglund P; Quertermous T 《Blood》1988,72(5):1833-1836
Glanzmann thrombasthenia is an autosomal recessive disorder of the platelet glycoproteins (GP) IIb and IIIa. These glycoproteins normally serve as receptors for other adhesive glycoproteins, including fibrinogen, von Willebrand factor, and fibronectin. Most patients affected by Glanzmann thrombasthenia have low levels of GPIIb and GPIIIa; however, the separate mechanisms responsible for the deficiency in each remain to be determined. cDNA clones coding for the GPIIb and GPIIIa have been recently isolated, and their corresponding genomic sequences have been colocalized to the long arm of chromosome 17. Since a deletional event involving one or both of these structural genes could explain the disease phenotype, we have studied the DNA of two previously well-characterized cohorts of Glanzmann thrombasthenia patients from Israel. We performed Southern analysis with near full- length cDNA probes on genomic DNA obtained from 20 individuals. Four restriction enzyme digests were completed on each DNA sample. The similarity of banding patterns among probands, family members, and controls indicated that there were no major insertions or deletions in either the GPIIb or GPIIIa genes. Thus, the genetic defect in these patients with Glanzmann thrombasthenia is most likely due to either a small change in the nucleotide sequence of the coding region or a defect in the regulatory region of one or both genes. 相似文献
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JÉRÔME FRENETTE 《Journal of anatomy》2000,196(2):211-216
Morphological observations have shown previously that myotendinous junctions (MTJs) are sites where the associations between the cytoskeleton and the cell membrane are extensively remodelled during muscle growth and modified mechanical loading. The platelet derived growth factor (PDGF) molecule has been shown to induce cytoskeletal remodelling at focal contact sites of myoblasts in culture, the analogous structures of MTJs. The goals of the study were to determine whether PDGF is synthesised by mononuclear cells and whether PDGF receptors are internalised at the MTJs of the soleus muscle experiencing reloading. We also examined whether ED2+ macrophages that are nonphagocytic and activated inflammatory cells at MTJs during reloading secrete PDGF. Results obtained by immunohistochemistry showed that there was an increase in the number of cells expressing PDGF at remodelling MTJs and that the ED2+ macrophage population does not express PDGF at MTJs. According to morphological criteria, fibroblasts would be the logical candidates to secrete PDGF molecules near MTJs. Furthermore, the modification in muscle loading resulted in internalisation of PDGF receptors concentrated at the MTJ which accumulated predominantly around muscle nuclei. The enrichment of PDGF receptors and PDGF+ cells at MTJs and the internalisation of PDGF receptors during remodelling of MTJs suggest that PDGF may influence remodelling of MTJs following modified muscle use. 相似文献
999.
目的探讨肾活组织病理检查(下称肾活检)在肾病综合征诊治中的意义。方法选择近10年诊断为肾病综合征患者1009例,分析肾活组织穿刺检查术后的病理结果。结果原发性肾小球肾炎占71.9%,病理类型以非IgA系膜增生性肾炎、IgA肾病及膜性肾病多见;继发性肾病综合征占28.1%,其中居前3位的是狼疮性肾炎、过敏性紫癜性肾炎和乙肝病毒相关性肾炎。结论肾活检对肾病综合征的诊断、治疗及评估预后有重要意义。 相似文献
1000.