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Studies of proteins that inhibit tissue factor activity have generally been conducted using either an extracted tissue homogenate ("thromboplastin") or tissue factor protein reconstituted into phospholipid vesicles rather than with tissue factor expressed in cell membranes (its physiological environment). In the present study, a human fibroblast cell strain was used to evaluate the effects of lipoprotein associated coagulation inhibitor (LACI), placental anticoagulant protein (PAP), and apolipoprotein A-II (apo A-II) on human tissue factor in cell membranes. LACI was tested from 7.8 to 500 pmol/L on fibroblasts cultured at cell densities ranging from 3,500 to 9,925 cells/well, and caused a progressive inhibition of tissue factor activity. PAP was tested from 3.9 nmol/L to 1 mumol/L at cell densities ranging from 4,500 to 15,400 cells/well and caused up to 83% inhibition of tissue factor activity. Inhibition by these proteins appeared to be influenced by cell density as well as whether the cells were intact or disrupted. Apo A-II, up to 1 mumol/L, did not inhibit the tissue factor activity of intact or disrupted fibroblasts at any cell density examined even though it did inhibit the activity of tissue factor in phospholipid vesicles. Of these inhibitors of tissue factor-dependent activation of factor X, LACI was the most effective in suppressing the generation of factor Xa activity. The effects obtained with apo A-II are clearly dependent on the nature of the tissue factor preparation with which it is tested. The disparity between the inhibitory effect of apo A-II on the activity of tissue factor reconstituted into lipid vesicles and the absence of effect on the activity of tissue factor remaining in cell membranes serves to reemphasize the necessity of reexamining results obtained with model systems using as nearly physiological reagents as possible. 相似文献
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Myosin VIIA gene: heterogeneity of the mutations responsible for Usher syndrome type IB 总被引:8,自引:1,他引:8
Levy G; Levi-Acobas F; Blanchard S; Gerber S; Larget-Piet D; Chenal V; Liu XZ; Newton V; Steel KP; Brown SD; Munnich A; Kaplan J; Petit C; Weil D 《Human molecular genetics》1997,6(1):111-116
Usher syndrome is recognized as the most frequent cause of hereditary
deaf-blindness. Usher syndrome type I (USH1), the most severe form of the
disease, is characterized by profound congenital sensorineural deafness,
constant vestibular dysfunction, and retinitis pigmentosa of prepubertal
onset. This form is genetically heterogeneous and five loci (USH1A-E) have
been mapped thusfar. However, only the gene responsible for USH1 B (which
accounts for approximately 75% of USH1 cases) has been characterized. It
encodes a long-tailed unconventional myosin, myosin VIIA, with a predicted
2215 amino acid sequence. Primers covering the complete myosin VIIA coding
sequence as well as the 3' non coding sequence were designed, allowing
direct sequence analysis of each of the 48 coding exons and flanking splice
sites in seven patients affected by USH1. Four novel mutations were thereby
identified. The possibility should now be considered of a sequence-based
prenatal diagnosis in some of the families affected by this very severe
form of Usher syndrome.
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Evolutionary silencing of the human elastase I gene (ELA1) 总被引:6,自引:0,他引:6
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Venkat Boddapati Michael B. Held Matthew Levitsky Ryan S. Charette Alexander L. Neuwirth Jeffrey A. Geller 《The Journal of arthroplasty》2021,36(6):2049-2054.e5
BackgroundTreatment options for metastatic osseous lesions of the proximal femur include hemiarthroplasty (HA) or total hip arthroplasty (THA) depending on lesion characteristics and patient demographics. Studies assessing short-term outcomes after HA/THA in this patient population are limited. Therefore, the purpose of this present study was to identify short-term rates of morbidity and mortality after HA/THA for pathological proximal femur fractures, as well as readmission and reoperation rates and reasons.MethodsThis study utilized a large, prospectively collected registry to identify patients who underwent HA/THA between 2011 and 2018. Patients were stratified by indication for surgery, including pathological fracture, nonpathological fracture, and osteoarthritis. Baseline patient characteristics and postoperative complications were compared using bivariate and/or multivariate analysis.ResultsIn total, 883 patients undergoing HA/THA for a pathological fracture were identified. Relative to an osteoarthritis cohort, these patients tended to be older, had a lower body mass index, and had significantly more preoperative comorbidities. These patients had high rates of total complications (13.93%), including thirty-day mortality (3.29%), unplanned return to the operating room (4.98%), and pulmonary complications (3.85%). Patients with pathological fracture had a longer operative duration relative to osteoarthritis and nonpathological cohorts (+27 and +25 minutes, respectively), despite having high rates of HAs performed.ConclusionPatients undergoing hip arthroplasty for pathologic proximal femur fracture have increased morbidity and mortality relative to an osteoarthritis cohort. However, patients with a pathological fracture have similar rates of morbidity and mortality when compared with a nonpathological fracture cohort, but did experience higher rates of perioperative blood transfusion and unplanned readmissions.Level of EvidenceIII. 相似文献