The Apple 1 and Apple 4 domains of factor XI act synergistically to promote the surface-mediated activation of factor XI by factor XIIa

Binding sites for high molecular weight kininogen (HK) and for factor XIIa are present in the Apple 1 (A1) and the A4 domains of factor XI, respectively. To define the roles of these two sites in surface- mediated factor-XI activation we prepared conformationally constrained synthetic peptides and recombinant A1 domain (rA1) and determined their effects on the activation of factor XI by factor XIIa in the presence of HK and either kaolin or dextran sulfate. Surface-mediated factor-XI activation by factor XIIa was inhibited by a conformationally constrained A4 peptide (Ala317-Gly350), by an A1 peptide (Phe56-Ser86), and by rA1 (Glu1-Ser90). When used in combination at equimolar concentrations, rA1 and A4 peptide were 10-fold more effective than either one alone in inhibiting surface-mediated activation of factor XI by factor XIIa. The A4 peptide was a competitive inhibitor of factor XIIa amidolytic activity and a noncompetitive inhibitor of factor-XI activation by factor XIIa, whereas rA1 and the A1 peptide did not inhibit factor XIIa. The rA1 domain inhibited factor XI binding to HK, whereas the A4 peptide did not. We conclude that specific sequences exposed on the surfaces of the A1 (Val59-Lys83) and A4 (Ala317-Gly350) domains of factor XI act synergistically to promote surface-mediated factor-XI activation by factor XIIa in the presence of HK by binding factor XI to surface-bound HK (A1 domain) and by binding factor XIIa near the cleavage site (Arg369-Ile370) of factor XI (A4 domain).     

Progression of joint damage in early active severe rheumatoid arthritis during 18 months of treatment: comparison of low-dose cyclosporin and parenteral gold

OBJECTIVE: This study compared the progression of joint damage in patients with early active severe rheumatoid arthritis (RA) treated with cyclosporin or parenteral gold. METHODS: In this open, randomized, multicentre study with a blinded radiological endpoint, 375 patients who had suffered from active severe RA for <3 yr were randomized to be treated for 18 months with low-dose cyclosporin or parenteral gold. The groups were stratified with regard to corticosteroid use. Primary efficacy variables were numbers of erosions, erosion score and the Larsen-Dale joint damage score. RESULTS: Joint damage progressed at similar rates in both treatment arms. In both groups, patients receiving corticosteroids had less X-ray progression. Rheumatoid factor positivity, high swollen joint count, high erythrocyte sedimentation rate and pre-existing X-ray abnormalities predicted progression of joint damage. Although numbers of serious adverse events were similar, more gold patients (n = 65) than cyclosporin patients (n = 45) withdrew from study medication because of adverse events. CONCLUSION: Cyclosporin was comparable to parenteral gold in retarding progression of joint damage and was better tolerated in terms of adherence to therapy. The open label design should be kept in mind when assessing this difference.      

Bone marrow donor registries: the relation between registry size and probability of finding complete and partial matches [see comments]

In a registry of volunteer bone marrow donors, the relation between registry size and probability of finding an exact or partial match for a random recipient cannot be theoretically derived because it depends on specifics of the human leukocyte antigen (HLA) haplotype frequencies in the donor and recipient populations. The relation must be explicitly calculated using empirically determined HLA haplotype frequency data for all possible pairings between a donor and a recipient population. This report describes a general solution to this problem. The method shows that the relation of the probability of matching to registry size is sigmoidal, with small increases in probability at the extremes of registry size and a middle range of registry size within which the probability of matching increases most sharply. This range determines the approximate size of the most cost-effective registry. In addition, for any pairing of donor and recipient populations, there is a maximum probability of identifying a match of a given quality for a random recipient, which cannot be exceeded even if registry size were infinite. This upper limit is a function of the frequency of blank (or unknown) alleles in the donor and recipient populations; the higher that frequency, the lower the maximum probability of achieving any given quality of match. The determinants of the probability of achieving a given quality of match with a given registry size are (1) the genetic heterogeneity within the recipient and donor populations, which increases the registry size required to achieve a given probability of matching, and (2) the degree of genetic homology between the donor and recipient populations, which increases the maximum probability of matching and also lowers registry size requirements. The method described here can be used to estimate donor pool size requirements using any donor and recipient populations for which HLA frequency data are available.     

Investigation of the role of von Willebrand factor in thrombotic thrombocytopenic purpura

Von Willebrand factor (vWF) has been implicated to function as a cofactor in platelet aggregation induced by thrombotic thrombocytopenic purpura (TTP) plasma. To investigate further this role of vWF, we have used rabbit monospecific anti-FVIII/vWF antibodies and a monoclonal antibody to platelet glycoprotein Ib (GP Ib) that blocks the ristocetin- induced platelet aggregation. The monoclonal anti-platelet GP Ib antibody inhibited the platelet aggregation induced by ristocetin in the presence of normal plasma, but not that by any of the five TTP plasma samples. The TTP plasma samples from five patients were incubated with the monospecific antibodies to FVIII/vWF. In all of the samples, the FVIII/vWF:Ag was drastically reduced; however, there was almost no effect on the platelet-aggregating activity. Therefore, it is concluded that vWF is unlikely to play a major role in platelet aggregation induced by majority of TTP plasmas and that the site of platelet GP Ib, to which vWF binds in the presence of ristocetin, is not involved in TTP plasma-induced aggregation.     

脱中性粒细胞温血心脏停搏液连续灌注在心脏手术中心肌保护的研究

目的 :研究体外循环期间常温血脱中性粒细胞心脏停搏液微流量连续灌注对心脏瓣膜置换术中心肌的保护作用。方法 :临床随机选取体外循环时间在 60min以上的风湿性心脏瓣膜病人 2 0例 ,随机分为实验组和对照组 (每组 10例 ) ,分别检测不同时间点血浆心肌肌钙蛋白I(cTnI)水平和血浆MDA水平的变化。结果 :①两组病人在CPB前cTnI含量组间差异无显著性 ,而在主动脉阻断后及主动脉开放后各时间点差异显著 ,对照组cTnI值高于实验组 (P <0 .0 5 ) ;②两组病人在体外循环前及主动脉阻断 3 0min时MDA的含量组间差异无显著性 ,而在主动脉开放各时间点组间差异具有显著性 (P <0 .0 5 ) ,对照组高于实验组。结论 :实验研究证实 ,脱除心脏停搏液中的中性粒细胞后 ,可减轻中性粒细胞介导的心肌损伤 ,有利于心肌保护     

Incest diagnosis by comparison of alleles of mother and offspring at highly heterozygous loci

BACKGROUND: Methods that detect a child's homozygosity by examination of allelic products are insensitive for diagnosing incest because, at a given locus, a homozygous state is expected with a frequency of only 0.25 when parents are first-degree relatives. Furthermore, these methods are not specific if the population contains many homozygous individuals or silent alleles that cause apparent homozygosity. STUDY DESIGN AND METHODS: Use of highly heterozygous loci improves specificity, but not sensitivity. Sensitivity may be increased by observing for two kinds of mother-offspring similarities: an offspring of incest tends to be homozygous or heterozygous-identical with respect to its mother's phenotype. At each locus, two conditional probabilities may be calculated for a genetic observation, using allele frequencies expected under a state of incestuous mating versus mating within a specified population. The conditional probabilities at each locus are compared in a likelihood ratio to express a relative probability of incest. RESULTS: In a case of known sibling incest, three likelihood ratios were derived from variable number of tandem repeat phenotypes at five loci. When only offspring homozygosity was observed, the likelihood ratio was 75.3:1. When both homozygous- and heterozygous- identical phenotype similarities of offspring and mother were noted, the likelihood ratio was 130.4:1. When maternal obligatory alleles of the offspring were considered, the likelihood ratio was 262.4:1. CONCLUSION: Comparison of maternal and offspring phenotypes at highly heterozygous loci increases both sensitivity and specificity of genetic tests in cases of suspected incest.     

医用壳聚糖创面修复膜凝胶在面部外伤患者中的应用效果

目的 分析医用壳聚糖创面修复膜凝胶在面部外伤患者临床治疗中的应用效果。方法 选择2020年 1月-2022年12月我院收治的50例面部外伤患者为研究对象，采用随机数字表法分为对照组和试验组，每组 25例。对照组给予面部伤口常规处理，试验组在对照组基础上给予医用壳聚糖创面修复膜凝胶，比较两组 面部伤口愈合情况、临床疗效、面部伤口细菌情况。结果 试验组面部伤口愈合率为100.00%，高于对照组 的84.00%，差异有统计学意义（P＜0.05）；试验组治疗总有效率为100.00%，高于对照组的84.00%，差异有 统计学意义（P＜0.05）；试验组治疗第3、5天伤口细菌数量＜1 cfu/cm2占比高于对照组，1 cfu/cm2＜伤口 细菌数量＜10 cfu/cm2占比低于对照组，差异有统计学意义（P ＜0.05）。结论 医用壳聚糖创面修复膜凝胶 在面部外伤患者中的应用效果确切，能够有效促进面部伤口愈合，抑制细菌生长，避免伤口感染、开裂迹 象，值得临床应用。     

AsC不同中医体质人群“伏邪”之探析

无症状慢性乙肝病毒携带者(AsC)在临床上没有明显的症状和体征,然其在感染乙型肝炎病毒(HBV)后患者可长期无症状携带,并伴随不同程度的肝损伤.因此从“伏邪”学说出发对不同体质AsC人群的邪气藏伏和发病机理进行理论探讨,对临床预防AsC人群发病具有理论指导意义.