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Inactivation of factor XIa in human plasma assessed by measuring factor XIa-protease inhibitor complexes: major role for C1-inhibitor 总被引:3,自引:1,他引:2
Wuillemin WA; Minnema M; Meijers JC; Roem D; Eerenberg AJ; Nuijens JH; ten Cate H; Hack CE 《Blood》1995,85(6):1517-1526
From experiments with purified proteins, it has been concluded that factor XIa (FXIa) is inhibited in plasma mainly by alpha 1-antitrypsin (a1AT), followed by antithrombin III (ATIII), C1-inhibitor (C1Inh), and alpha 2-antiplasmin (a2AP). However, the validity of this concept has never been studied in plasma. We established the relative contribution of different inhibitors to the inactivation of FXIa in human plasma, using enzyme-linked immunosorbent assays (ELISAs) for the quantification of complexes of FXIa with a1AT, C1Inh, a2AP, and ATIII. We found that 47% of FXIa added to plasma formed complexes with C1Inh, 24.5% with a2AP, 23.5% with a1AT, and 5% with ATIII. The distribution of FXIa between these inhibitors in plasma was independent of whether FXIa was added to plasma, or was activated endogenously by kaolin, celite, or glass. However, in the presence of heparin (1 or 50 U/mL), C1Inh appeared to be the major inhibitor of FXIa, followed by ATIII. Furthermore, at lower temperatures, less FXIa-C1Inh and FXIa-a1AT complexes but more FXIa-a2AP complexes were formed. These data demonstrate that the contribution of the different inhibitors to inactivation of FXIa in plasma may vary, but C1Inh is the principal inhibitor under most conditions. 相似文献
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BACKGROUND: The effect of prestorage filtration on the quality of apheresis platelet concentrates stored for transfusion is undetermined. STUDY DESIGN AND METHODS: Investigation of 11 plateletpheresis components used a concurrent paired-study design. On the day of collection, each component was equally divided into two suspensions; one half was filtered, and the other half was not. Each suspension was stored for 5 days. In vitro testing was performed on the day of collection (Day 0) for cell counts and on Day 5 for measurements of lactate, glucose, blood gases, pH, platelet ATP, hypotonic stress ratio, extent of shape change in response to ADP, tissue necrosis factor alpha, interleukin 8, interleukin 1 alpha, interleukin 1 beta, interleukin 6, and platelet surface glycoproteins by flow cytometry. At the end of the 5-day period, a sample was taken from each of the two suspensions, radiolabeled with either 51Cr or 111In, and transfused concurrently. Posttransfusion samples were drawn for measurements of recovery and platelet survival and for functional assessment of the ex vivo ability of the circulating radiolabeled platelets to aggregate in response to ADP. RESULTS: The apheresis component had a mean platelet yield of 3.2 +/? 0.4 × 10(11) and a white cell yield ranging from 1 × 10(5) to 1 × 10(8), with a median of 2 × 10(7). Filtration resulted in a platelet loss of approximately 10 percent and a variable 2 to 3 log10 reduction in white cell content. No significant differences between filtered and unfiltered suspensions in paired t tests that would likely have an impact on platelet quality were observed in the in vitro tests. The in vivo recovery and survival were highly similar and not statistically different in filtered and unfiltered paired suspensions: the mean difference was 1.2 +/? 4.0 percent for recovery and 7.0 +/? 15 hours for survival. The functional assessment by aggregation to ADP showed no difference between filtered and unfiltered suspensions. A small decrease in tumor necrosis factor alpha and interleukin 8 was evident in the filtered suspension as compared to levels in the unfiltered suspensions. CONCLUSION: Prestorage white cell reduction in apheresis components resulted in WBC reduction by several log10 with no evident adverse effect on platelet viability or function. 相似文献
76.
Induction of IL-5 expression by IL-2 is resistant to the immunosuppressive agents cyclosporin A and rapamycin 总被引:1,自引:0,他引:1
T cell cytokine expression may be induced by the cytokine IL-2 or via the
TCR complex. The comparative effects of cytokine- and TCR-mediated
signalling on the induction of human IL-5 mRNA were examined. Cytokine mRNA
expression was analysed by RT-PCR in fresh peripheral blood mononuclear
cells (PBMC) from normal individuals and in populations of activated T
lymphocytes, derived from phytohaemagglutinin (PHA)- stimulated PBMC. rIL-2
induced IL-5 expression in PBMC, the kinetics of which were similar to the
effects of PHA. rIL-4 induced IL-5 mRNA expression in activated T
lymphocytes. IL-5 expression induced by either IL-2 or PHA was completely
abolished by the protein synthesis inhibitor cycloheximide. rIL-2-induced
IL-5 expression was resistant to cyclosporin A (CsA), whereas IL-5
expression elicited by PHA was inhibited by CsA, at doses as low as 10
ng/ml. Rapamycin (RAP) had no effect on rIL-2-stimulated IL-5 expression,
but suppressed IL-5 expression induced by PHA. The inhibitory effect of RAP
on PHA-induced IL-5 expression was more apparent at 12 and 24 h after
stimulation than at earlier times. The resistance of IL-2 receptor (IL-2R)
signalling to CsA and RAP indicates that the IL-2R and the TCR are
associated with different pathways regulating IL-5 expression.
相似文献
77.
X-linked hypophosphatemia in adults: prevalence of skeletal radiographic and scintigraphic features 总被引:3,自引:0,他引:3
The radiologic studies of 38 essentially untreated adults with X-linked hypophosphatemia (XLH) were reviewed to determine the prevalence of radiologic features, to compare the findings in men and in women, and to elucidate the natural history of the disease by comparing the findings in young, intermediate-age, and older patients. Bone-reinforcement lines were common, but no characteristic mineral mass alteration was established. Looser zones were more prevalent in older subjects. Osteoarthritis was common, occurring in the ankles, knees, feet, sacroiliac joints, and wrists. Enthesopathy was infrequent in the younger group but was present in every member of the intermediate and older groups and was often accompanied by extra ossicles. Curvatures of the lower-extremity long bones were common in all age groups. Three new skeletal alterations in XLH were found to be common: flaring of the iliac wings, trapezoidal distal femoral condyles, and alterations in talar morphology, including shortening of the talar neck and flattening of the talar dome. Technetium-99m methylene diphosphonate scintigrams of 17 subjects were often abnormal, depicting bowing deformity and focal tracer accumulation in diaphyseal cortices and in periarticular and extraarticular regions. The mean metabolic index was moderately elevated (4.0). Both radiographic and scintigraphic findings were more severe in men, consistent with hemizygosity. The natural history of untreated XLH in both sexes is characterized by the development of a variety of age-related skeletal abnormalities during adulthood. 相似文献
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DAO JIE LIU YING LIU ZHUO LI YAN YAN JI MING YIN WA HAO JIN QIN NIU FANG LIU XIAN CHUN XIE HUI LI 《中华微生物学和免疫学杂志(英文版)》2007,5(2):133-138
The aim of this study is to investigate whether three mononucleotide polymorphisms at the locus -1082,-819 and -592 in the promoter region of the IL-10 gene are associated with chronic severe hepatitis. The IL-10-592 and IL-10-1082 polymorphisms were genotyped by polymerase chain reactionrestriction fragment length polymorphism analysis (PCR-RFLP) while polymerase chain reaction-sequence specific primer (PCR-SSP) assay was used to test the IL-10-819 polymorphism. The polymorphisms of IL-10-1082, -819 and -592 genes were detected in 98 patients with chronic severe hepatitis (CSH), 478 patients with chronic hepatitis B (CHB), 223 asymptomatic (chronic) HBV carriers (ASC) and 267 patients with self-restricted HBV. There was significant difference of the polymorphisms of IL-10-1082, IL-10-819 and IL-10-592 genes between CSH group and other groups. The frequency of AA genotype at IL-10 gene promoter -1082 locus in chronic severe hepatitis patients was higher than that in asymptomatic HBV carriers (2 = 13. 314, P = 0.001), and self-restricted HBV patients (χ^2 = 13.545, P = 0.000); the frequency of CC and AC genotype at IL-10 gene promoter -592 locus in chronic severe hepatitis patients was higher than that in chronic hepatitis patients(χ^2 = 15.970, P=0.000) (χ^2 =20.414, P=0.000), asymptomatic HBV carriers (χ^2 =21.283, P= 0.000) (χ^2 = 28.309, P = 0.000) and self-restricted HBV patients(χ^2 = 17.047, P = 0.000) (χ^2 = 16.528, P = 0.000) ; the frequency of TC genotype at IL-10 gene promoter -819 locus in chronic severe hepatitis patients was higher than that in chronic hepatitis patients(χ^2 = 58.961, P = 0.000), asymptomatic HBV carriers ( χ^2 = 53. 255, P = 0. 001 ) and self-restricted HBV patients (χ^2 = 39.616, P = 0.001). So interleukine-10 gene polymorphism was associated with the chronic severe hepatitis. 相似文献