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Molecular characterization of human factor XSan Antonio 总被引:1,自引:0,他引:1
Enzymatic amplification technique was used to isolate all eight exons and sequences around the splice junctions, putative promoter, and polyadenylation sites of human factor X DNA from a patient with factor X deficiency. Two genetic changes in factor X have been observed in this patient. The patient is most likely a compound heterozygote since there is only 14% activity associated with factor X. A point mutation that resulted in the substitution of cysteine (TGC) for arginine (CGC) at amino acid 366 was found in exon VIII of one allele of the factor X gene. This mutation, which occurs in the catalytic domain, can affect the formation of a disulfide bridge and thus could result in a reduction in factor X activity. Sequencing all the regions revealed a second mutation: a deletion of one nucleotide (TCCT to TCT) in exon VII that would cause a frame shift at amino acid 272 followed by termination. We have also shown that the point mutation in exon VIII creates an ApaL1 restriction site and destroys the HinP1 site. Enzymatic DNA amplification followed by restriction digestion provides a quick, reliable, and sensitive method for carrier detection and antenatal diagnosis in affected kindreds. This is the first characterization of factor X deficiency at the molecular level. We propose to name this mutation Factor XSan Antonio. 相似文献
33.
Activation of the coagulation cascade after infusion of a factor XI concentrate in congenitally deficient patients 总被引:5,自引:1,他引:5
Mannucci PM; Bauer KA; Santagostino E; Faioni E; Barzegar S; Coppola R; Rosenberg RD 《Blood》1994,84(4):1314-1319
Virally inactivated, high-purity factor XI concentrates are available for treatment of patients with factor XI deficiency. However, preliminary experience indicates that some preparations may be thrombogenic. We evaluated whether a highly purified concentrate produced signs of activation of the coagulation cascade in two patients with severe factor XI deficiency infused before and after surgery. Signs of heightened enzymatic activity of the common pathway of coagulation (elevated plasma levels of prothrombin fragment 1 + 2 and fibrinopeptide A) developed in the early post-infusion period, accompanied by more delayed signs of fibrin formation with secondary hyperfibrinolysis (elevated D-dimer and plasmin-antiplasmin complex). These changes occurred in both patients, but were more severe in the older patient with breast cancer when she underwent surgery, being accompanied by fibrinogen and platelet consumption. There were no concomitant signs of heightened activity of the factor VII-tissue factor mechanism on the factor Xase complex (plasma levels of activated factor VII and of factor IX and X activation peptides did not increase). The observed changes in biochemical markers of coagulation activation indicate that concentrate infusions increased thrombin generation and activity and that such changes were magnified by malignancy and surgery. Because some factor XI concentrates may be thrombogenic, they should be used with caution, especially in patients with other risk factors for thrombosis. 相似文献
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目的分析先天性肠闭锁病例的诊断及治疗,以提高治愈率及术后生活质量。方法回顾性分析166例先天性肠闭锁的临床资料。结果治愈142例,治愈率85.5%(142/166),其中包括18例二期手术治愈者;术中10例、术后8例放弃治疗;术后死亡6例。结论早期诊断和选择合理的术式是提高肠闭锁治愈率的关键,基础支持及手术技术改进能促进病情的恢复,改善预后。 相似文献
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Analogues of oxytocin and deaminooxytocin with 4-glutamine replaced by 4-glutamic acid methyl ester readily lose their uterotonic activity when incubated with rat serum, presumably by hydrolysis to the much less active 4-glutamic acid derivatives. On the other hand, inactivation of the deaminooxytocin analogue in the rat uterus, as demonstrated by the 'oil-bath'technique, is only slightly more rapid than that of deaminooxytocin and distinctly slower than that of oxytocin. Its in situ/in vitro ratio of uterotonic activity is less than 0.1 whereas that for deaminooxytocin is about 3 and also the persistence of the uterotonic effect in situ is slightly less than that of deaminooxytocin. The results with these 'rapidly inactivated'analogues can be used as proof of some predictions of the three-compartment model for tissue distribution of neurohypophysial hormones and its influence upon the time course of a biological response published earlier. The potential use of analogues of neurohypophysial hormones as probes for inactivation mechanisms and the results thus far obtained are discussed. 相似文献
39.
Goldie SJ Kuntz KM Weinstein MC Freedberg KA Palefsky JM 《The American journal of medicine》2000,108(8):634-641
PURPOSE: Homosexual and bisexual men are at an increased risk for human papillomavirus-induced squamous intraepithelial lesions and cancer of the anus. Our objective was to estimate the cost-effectiveness of screening for anal squamous intraepithelial lesions in these high-risk patients. SUBJECTS AND METHODS: A Markov model was developed to evaluate alternative screening strategies using anal cytology in a hypothetical cohort of homosexual and bisexual men. Data were obtained from prospective cohort studies, national databases, Medicare reimbursement rates, and the published literature. Model outcomes included life expectancy, quality-adjusted life expectancy, total lifetime costs, and incremental cost-effectiveness ratios. RESULTS: The undiscounted life expectancy gain associated with anal cytology screening every 3 years was 5.5 months. Compared with no screening, screening every 3 years increased the discounted quality-adjusted life expectancy by 1.8 months and cost $7,000 per quality-adjusted life year (QALY) gained. Screening every 2 years cost $15,100 per QALY gained compared with screening every 3 years. Annual screening provided incremental benefits of less than 0.5 quality-adjusted months and had an incremental cost of $34,800 per QALY gained. Screening every 6 months provided little additional benefit (i.e, 5 days) over that of annual screening and had an incremental cost of $143,500 per QALY gained. CONCLUSION: In homosexual and bisexual men, screening every 2 or 3 years for anal squamous intraepithelial lesions with anal cytology would provide life-expectancy benefits comparable with other accepted preventive health measures, and would be cost-effective. 相似文献
40.
Two patients with hairy cell leukemia with massive splenomegaly and severe pancytopenia were treated with recombinant alpha-A interferon (IFN-alpha-2a). There was no significant response to a trial of IFN- alpha-2a (11 and 20 weeks) with respect to blood counts or spleen size. Subsequent treatment with 2'-deoxycoformycin (dCF) for 8 consecutive weeks (4 mg/m2/wk) resulted in normalization of spleen size and a normalization of peripheral blood counts and bone marrow in one patient. The second patient demonstrated a reduction in spleen size and improved blood counts following 9 weeks of dCF therapy but eventually became refractory. This demonstrates that dCF is non-cross-resistant with interferon and confirms the efficacy of dCF in nonsplenectomized patients. 相似文献