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91.
Inhibition of the intrinsic factor X activating complex by protein S: evidence for a specific binding of protein S to factor VIII 总被引:4,自引:2,他引:2
Protein S is a vitamin K-dependent nonenzymatic anticoagulant protein that acts as a cofactor to activated protein C. Recently it was shown that protein S inhibits the prothrombinase reaction independent of activated protein C. In this study, we show that protein S can also inhibit the intrinsic factor X activation via a specific interaction with factor VIII. In the presence of endothelial cells, the intrinsic activation of factor X was inhibited by protein S with an IC50 value of 0.28 +/- 0.04 mumol/L corresponding to the plasma concentration of protein S. This inhibitory effect was even more pronounced when the intrinsic factor X activation was studied in the presence of activated platelets (IC50 = 0.15 +/- 0.02 mumol/L). When a nonlimiting concentration of phospholipid vesicles was used, the plasma concentration of protein S (300 nmol/L) inhibited the intrinsic factor X activation by 40%. Thrombin-cleaved protein S inhibited the endothelial cell-mediated factor X activation with an IC50 similar to that of native protein S (0.26 +/- 0.02 mumol/L). Protein S in complex with C4b-binding protein inhibited the endothelial cell-mediated factor X activation more potently than protein S alone (IC50 = 0.19 +/- 0.03 mumol/L). Using thrombin activated factor VIII, IC50 values of 0.53 +/- 0.09 mumol/L and 0.46 +/- 0.10 mumol/L were found for native protein S and thrombin-cleaved protein S, respectively. The possible interactions of protein S with factor IXa, phospholipids, and factor VIII were investigated. The enzymatic activity of factor IXa was not affected by protein S, and interaction of protein S with the phospholipid surface could not fully explain the inhibitory effect of protein S on the factor X activation. Using a solid-phase binding assay, we showed a specific, saturable, and reversible binding of protein S to factor VIII with a high affinity. The concentration of protein S where half-maximal binding was reached (B1/2max) was 0.41 +/- 0.06 mumol/L. A similar affinity was found for the interaction of thrombin-cleaved protein S with factor VIII (B1/2max = 0.40 +/- 0.04 mumol/L). The affinity of the complex protein S with C4B-binding protein appeared to be five times higher (B1/2max = 0.07 +/- 0.03 mumol/L). Because the affinities of the interaction of the different forms of protein S with factor VIII correspond to the IC50 values observed for the intrinsic factor X activating complex, the interaction of protein S with factor VIII may explain the inhibitory effect of protein S on the intrinsic factor X activating complex.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
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RA Schwartz†‡ TM Bridges§ AK Butani† A Ehrlich§ 《Journal of the European Academy of Dermatology and Venereology》2008,22(5):606-615
Solar ultraviolet light electromagnetic waves are a known environmental carcinogenic agent closely associated with the development of skin cancer in light‐complexioned individuals. Outdoor workers have higher annual exposure to ultraviolet light. We will review the topic of actinic keratoses among these individuals as this common rudimentary form of superficial cutaneous squamous cell carcinoma is explored in greater detail. 相似文献
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Son N Do Chinh Q Luong Dung T Pham Chi V Nguyen Tra T Ton Thao TN Pham Quoc TA Hoang Hanh T Hoang Dat T Nguyen Dai Q Khuong Quan H Nguyen Tuan A Nguyen Hanh TM Pham My H Nguyen Bryan F McNally Marcus EH Ong Anh D Nguyen 《Bulletin of the World Health Organization》2021,99(1):50
ObjectiveTo investigate factors associated with survival after out-of-hospital cardiac arrest in Viet Nam.MethodsWe did a multicentre prospective observational study of people (> 18 years) presenting with out-of-hospital cardiac arrest (not caused by trauma) to three tertiary hospitals in Viet Nam from February 2014 to December 2018. We collected data on characteristics, management and outcomes of patients with out-of-hospital cardiac arrest and compared these data by type of transportation to hospital and survival to hospital admission. We assessed factors associated with survival to admission to and discharge from hospital using logistic regression analysis.FindingsOf 590 eligible people with out-of-hospital cardiac arrest, 440 (74.6%) were male and the mean age was 56.1 years (standard deviation: 17.2). Only 24.2% (143/590) of these people survived to hospital admission and 14.1% (83/590) survived to hospital discharge. Most cardiac arrests (67.8%; 400/590) occurred at home, 79.4% (444/559) were witnessed by bystanders and 22.3% (124/555) were given cardiopulmonary resuscitation by a bystander. Only 8.6% (51/590) of the people were taken to hospital by the emergency medical services and 32.2% (49/152) received pre-hospital defibrillation. Pre-hospital defibrillation (odds ratio, OR: 3.90; 95% confidence interval, CI: 1.54–9.90) and return of spontaneous circulation in the emergency department (OR: 2.89; 95% CI: 1.03–8.12) were associated with survival to hospital admission. Hypothermia therapy during post-resuscitation care was associated with survival to discharge (OR: 5.44; 95% CI: 2.33–12.74).ConclusionImprovements are needed in the emergency medical services in Viet Nam such as increasing bystander cardiopulmonary resuscitation and public access defibrillation, and improving ambulance and post-resuscitation care. 相似文献
98.
KA Jackman AA Miller TM De Silva PJ Crack GR Drummond CG Sobey 《British journal of pharmacology》2009,156(4):680-688
Background and purpose:
Reactive oxygen species (ROS) derived from Nox2-containing reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity is reportedly detrimental in cerebrovascular disease. However, ROS generation by other Nox isoforms may have a physiological role. No Nox2-selective inhibitors have yet been identified, and thus it is unclear whether isoform non-selective Nox inhibitors would necessarily improve outcome after stroke. We assessed the effect of apocynin on cerebrovascular ROS production and also on outcome following cerebral ischaemia when administered either before ischaemia or after cerebral reperfusion. The involvement of Nox2-containing NADPH oxidase in the effects of apocynin was assessed using Nox2−/− mice.Experimental approach:
Transient cerebral ischaemia was induced by 0.5 h middle cerebral artery occlusion followed by 23.5 h reperfusion. Mice received apocynin (2.5 mg·kg−1, i.p.) either 0.5 h before ischaemia or 1 h after reperfusion. In situ superoxide production after cerebral ischaemia-reperfusion was measured in brain sections of wild-type mice at 24 h using dihydroethidium fluorescence.Key results:
Treatment with apocynin 0.5 h before ischaemia reduced total infarct volume, neurological impairment and mortality in wild-type but not Nox2−/− mice. Conversely, treatment with apocynin 1 h after initiation of reperfusion had no protective effect. Cerebral ischaemia and reperfusion increased superoxide production in the brain at 24 h, and pretreatment but not posttreatment with apocynin reduced superoxide levels.Conclusions and implications:
Apocynin improves outcome following stroke when administered before ischaemia in wild-type but not Nox2−/− mice. 相似文献99.
Raman Jay JE Heckman L Hinshaw S Best M Lubner DF Jarrard TM Downs SY Nakada FT Lee W Huang T Ziemlewicz 《Urologic oncology》2017,35(3):119
Purpose
Percutaneous biopsy obtained from a single location is prone to sampling error in large heterogeneous renal masses, leading to nondiagnostic results or failure to detect poor prognostic features. We evaluated the accuracy of percutaneous biopsy for large renal masses using a modified multi-quadrant technique vs. a standard biopsy technique.Materials and methods
Clinical and pathological data for all patients with cT2 or greater renal masses who underwent percutaneous biopsy from 2009 to 2014 were reviewed. The multi-quadrant technique was defined as multiple core biopsies from at least 4 separate solid enhancing areas in the tumor. The incidence of nondiagnostic findings, sarcomatoid features and procedural complications was recorded, and concordance between biopsy specimens and nephrectomy pathology was compared.Results
A total of 122 biopsies were performed for 117 tumors in 116 patients (46 using the standard biopsy technique and 76 using the multi-quadrant technique). Median tumor size was 10 cm (IQR: 8–12). Biopsy was nondiagnostic in 5 of 46 (10.9%) standard and 0 of 76 (0%) multi-quadrant biopsies (P = 0.007). Renal cell carcinoma was identified in 96 of 115 (82.0%) tumors and nonrenal cell carcinoma tumors were identified in 21 (18.0%). One complication occurred using the standard biopsy technique and no complications were reported using the multi-quadrant technique. Sarcomatoid features were present in 23 of 96 (23.9%) large renal cell carcinomas studied. Sensitivity for identifying sarcomatoid features was higher using the multi-quadrant technique compared to the standard biopsy technique at 13 of 15 (86.7%) vs. 2 of 8 (25.0%) (P = 0.0062).Conclusions
The multi-quadrant percutaneous biopsy technique increases the ability to identify aggressive pathological features in large renal tumors and decreases nondiagnostic biopsy rates. 相似文献100.
Anny JTP Peters Maja Micevska Scharf Francien TM van Driel Willy HM Jansen 《Globalization and health》2010,6(1):23
This study analyses the priorities of public donors in funding HIV prevention by either integrated condom programming or HIV
preventive microbicides and vaccines in the period between 2000 and 2008. It further compares the public funding investments
of the USA government and European governments, including the EU, as we expect the two groups to invest differently in HIV
prevention options, because their policies on sexual and reproductive health and rights are different. We use two existing
officially UN endorsed databases to compare the public donor funding streams for HIV prevention of these two distinct contributors.
In the period 2000-2008, the relative share of public funding for integrated condom programming dropped significantly, while
that for research on vaccines and microbicides increased. The European public donors gave a larger share to condom programming
than the United States, but exhibited a similar downward trend in favour of funding research on vaccines and microbicides.
Both public donor parties invested progressively more in research on vaccines and microbicides rather than addressing the
shortage of condoms and improving access to integrated condom programming in developing countries. 相似文献