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排序方式: 共有420条查询结果,搜索用时 562 毫秒
101.
102.
Normalization of markers of coagulation activation with a purified protein C concentrate in adults with homozygous protein C deficiency 总被引:4,自引:0,他引:4
Conard J; Bauer KA; Gruber A; Griffin JH; Schwarz HP; Horellou MH; Samama MM; Rosenberg RD 《Blood》1993,82(4):1159-1164
Homozygous or double heterozygous protein-C deficiency can present at birth with purpura fulminans or later in life with venous thrombosis. Two homozygous patients who had previously sustained thrombotic episodes were investigated at a time when they were asymptomatic and not receiving antithrombotic therapy. The plasma levels of protein-C antigen and activity in both individuals were approximately 20% of normal. We administered a highly purified plasma-derived protein C concentrate to these individuals and monitored levels of several markers of in vivo coagulation activation. Assays for protein-C activation (activated protein C and protein C activation peptide) showed a sustained increase from reduced baseline levels, whereas thrombin generation (as measured by prothrombin fragment F1 + 2) gradually decreased over about 24 hours into the normal range. These investigations provide direct evidence that protein C is converted to activated protein C in vivo, and that the protein-C anticoagulant pathway is a tonically active mechanism in the regulation of hemostatic system activation in humans. 相似文献
103.
Clinical diagnosis of hypersensitivity pneumonitis 总被引:5,自引:0,他引:5
Lacasse Y Selman M Costabel U Dalphin JC Ando M Morell F Erkinjuntti-Pekkanen R Muller N Colby TV Schuyler M Cormier Y;HP Study Group 《American journal of respiratory and critical care medicine》2003,168(8):952-958
The diagnosis of hypersensitivity pneumonitis (HP) is difficult and often relies on histopathology. Our objective was to identify diagnostic criteria and to develop a clinical prediction rule for this disease. Consecutive patients presenting a condition for which HP was considered in the differential diagnosis underwent a program of simple standardized diagnostic procedures. High-resolution computed tomography scan and bronchoalveolar lavage (BAL) defined the presence or absence of HP. Patients underwent surgical lung biopsy when the computed tomography scan, BAL, and other diagnostic procedures failed to yield a diagnosis. A cohort of 400 patients (116 with HP, 284 control subjects) provided data for the rule derivation. Six significant predictors of HP were identified: (1) exposure to a known offending antigen, (2) positive precipitating antibodies to the offending antigen, (3) recurrent episodes of symptoms, (4) inspiratory crackles on physical examination, (5) symptoms occurring 4 to 8 hours after exposure, (6) and weight loss. The area under the receiver operating characteristic curve was 0.93 (95% confidence interval: 0.90-0.95). The rule retained its accuracy when validated in a separate cohort of 261 patients. The diagnosis of HP can often be made or rejected with confidence, especially in areas of high or low prevalence, respectively, without BAL or biopsy. 相似文献
104.
整合蛋白α5亚基表达与肝癌恶性表型 总被引:3,自引:0,他引:3
目的探讨整合蛋白α5亚基与原发性肝癌的关系。方法应用免疫组化技术(ABC法)和Northernblot杂交检测整合蛋白α5亚基在原发性肝癌中的表达。结果发现在79例癌与癌周组织α5阳性率分别为32.9%和81.0%,两者间差异有显著性(P<0.01)。直径≤5cm的肝癌α5阳性率高于直径>10cm的肝癌(55.6%比10.0%,P<0.01),分化较好的肝癌α5阳性率高于分化不良者(40.6%比16.0%,P<0.05),已发生明确肝内转移(包括肝内播散和门静脉癌栓形成)的肝癌α5阳性率低于未发生肝内转移者(20.6%比42.2%,P<0.05)。α5亚基表达与患者年龄、血清甲胎蛋白水平、乙型肝炎病毒感染、肝硬化有无等因素均无明显相关(P>0.05)。Northernblot杂交结果也同时显示,非侵袭性肝癌α5表达高于侵袭性肝癌。结论整合蛋白α5低表达与肝癌增大、分化程度低、侵袭转移发生等恶性表型相关,可能对这些恶性表型起负性调节作用。 相似文献
105.
Plasma protein S deficiency in familial thrombotic disease 总被引:21,自引:2,他引:21
A family with a history of severe recurrent venous thromboembolic disease was studied to determine if a plasma protein deficiency could account for observed disease. Protein S levels in plasma were determined immunologically using the Laurell rocket technique. The propositus, his mother, his aunt, and his cousin who were clinically affected had 17% to 65% of the control levels of protein S antigen (normal range, 71% to 147%). Since three of these patients were receiving oral anticoagulant therapy, the ratios of protein S to prothrombin, factor X, and protein C in these patients were compared with values for a group of orally anticoagulated controls. These results suggested that protein S is half-normal in all family members with thrombotic disease. Other proteins known to be associated with familial thrombotic disease, including antithrombin III, plasminogen, fibrinogen, and protein C, were normal. Because plasma protein S serves as a cofactor for the anticoagulant activity of activated protein C and because protein C deficiency is associated with recurrent thrombotic disease, it is suggested that recurrent thrombotic disease in this family is the result of an inherited deficiency of protein S. 相似文献
106.
107.
Morosetti R; Grignani F; Liberatore C; Pelicci PG; Schiller GJ; Kizaki M; Bartram CR; Miller CW; Koeffler HP 《Blood》1996,87(10):4399-4403
Retinoids are important regulators of cell growth and differentiation in vitro and in vivo and they exert their biologic activities by binding to nuclear retinoic acid receptors (RARs; alpha, beta, and gamma) and retinoid X receptors (RXRs; alpha, beta, and gamma). All- trans retinoic acid (RA) induces complete remission in patients with acute promyelocytic leukemia (APL) presumably by binding directly to RAR alpha of APL cells. Leukemic blasts from APL patients initially responsive to RA can become resistant to the agent. HL-60 myeloblasts cultured with RA have developed mutations of the ligand-binding region of RAR alpha and have become resistant to RA. Furthermore, insertion of an RAR alpha with an alteration in the ligand-binding region into normal murine bone marrow cells can result in growth factor-dependent immortalization of the early hematopoietic cells. To determine if alterations of the ligand binding domain of RAR alpha might be involved in several malignant hematologic disorders, the mutational status of this region (exons 7, 8, and 9) was examined in 118 samples that included a variety of cell lines and fresh cells from patients with myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML), including 20 APL patients, 5 of whom were resistant to RA and 1 who was refractory to RA at diagnosis, using polymerase chain reaction-single- strand conformational polymorphism (PCR-SSCP) analysis and DNA sequencing. In addition, 7 of the 20 APLs were studied for alterations of the other coding exons of the gene (exons 2 through 6). No mutations of RAR alpha were detected. Although the sensitivity of PCR-SSCP analysis is less than 100%, these findings suggest that alterations of RAR alpha gene are rare and therefore other mechanisms must be involved in the onset of resistance to retinoids and in the lack of differentiation in disorders of the myeloid lineage. 相似文献
108.
Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) in primary effusion lymphoma: ultrastructural demonstration of herpesvirus in lymphoma cells 总被引:10,自引:1,他引:10
Said W; Chien K; Takeuchi S; Tasaka T; Asou H; Cho SK; de Vos S; Cesarman E; Knowles DM; Koeffler HP 《Blood》1996,87(12):4937-4943
Recent molecular evidence suggests an association with a new herpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8), and primary effusion lymphomas (PELs). PELs have a characteristic morphology, phenotype, and clinical presentation, with malignant effusions in the absence of a contiguous solid tumor mass. We have established a cell line (KS-1) from a KSHV-positive human immunodeficiency virus (HIV)-negative patient with pleural cavity-based lymphoma that was passaged into triple-immunodeficient BNX mice. In contrast to cell lines from body cavity-based lymphomas derived from HIV-positive individuals that contain both KSHV and Epstein Barr viral genome, these cells contain only KSHV, allowing for uncontaminated virologic studies. Ultrastructural examination identified malignant cells with features of late differentiating B cells (immunoblasts). Cells with viral cytopathic effect contained typical 110-nm intranuclear herpesvirus nucleocapsids and complete cytoplasmic virions, confirming the association of PEL with KSHV. 相似文献
109.
Synergistic effects of thrombopoietin and granulocyte colony- stimulating factor on neutrophil recovery in myelosuppressed mice 总被引:1,自引:0,他引:1
Grossmann A; Lenox J; Deisher TA; Ren HP; Humes JM; Kaushansky K; Sprugel KH 《Blood》1996,88(9):3363-3370
Severe suppression of the hematopoietic system is a major factor in limiting chemotherapy dose escalation. To determine whether a combination of human recombinant granulocyte colony-stimulating factor (G-CSF) and thrombopoietin (TPO) would alter recovery of platelets, red blood cells (RBCs), or neutrophils after myeloablative therapy, myelosuppressed mice were treated with sc injections of TPO (90 micrograms/kg), G-CSF (250 micrograms/kg). TPO plus G-CSF or vehicle and complete blood counts were measured. Marrow and spleen cells were obtained at various times and assayed for erythroid, myeloid, and megakaryocytic progenitors. The prolonged neutropenia in vehicle controls (14 days) was significantly shortened in mice treated with G- CSF or TPO for 14 days. The combination of TPO plus G-CSF further reduced the duration of neutropenia. TPO and TPO plus G-CSF treatments also significantly shortened thrombocytopenia compared to vehicle. Recovery of RBCs was also enhanced in mice treated with either G-CSF or TPO, or the combination. Furthermore, treatment with G-CSF and/or TPO hastened myeloid, erythroid, and megakaryocyte progenitor recovery compared to vehicle controls. These results show that the combination of TPO plus G-CSF acts synergistically to accelerate neutrophil recovery in myelosuppressed mice and does not compromise the platelet or RBC response to TPO therapy. 相似文献
110.
Sixt SU Jennissen HP Winterhalter M Laub M 《European journal of medical research》2010,15(10):428-447
The selective degradation of many proteins in eukaryotic cells is carried out by the ubiquitin system. In this pathway, proteins are targeted for degradation by covalent ligation to ubiquitin, a highly conserved protein [1]. Ubiquitylated proteins were degraded by the 26S proteasome in an ATP-depended manner. The degradation of ubiquitylated proteins were controlled by isopeptidase cleavage. A well characterised system of ubiquitylation and deubiquitylation is the calmodulin system in vitro [2]. Detection of ubiquityl-calmodulin conjugtates in vivo have not been shown so far. In this article we discuss the detection of ubiquitin calmodulin conjugates in vivo by incubation with a novel high-molecular weight ubiquitylprotein-isopeptidase in rabbit tissues. Proteins with a molecular weight of ubiquityl-calmodulin conjugates could be detected in all organs tested. Incubation with ubiquitylprotein-isopeptidase showed clearly a decrease of ubiquitin calmodulin conjugates in vivo with an origination of unbounded ubiquitin. These results suggest that only few ubiquitin calmodulin conjugates exist in rabbit tissues. 相似文献