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101.
D. Noone J. Al‐Matrafi K. Tinckam P. F. Zipfel A. M. Herzenberg P. S. Thorner F. G. Pluthero W. H. A. Kahr G. Filler D. Hebert E. Harvey C. Licht 《American journal of transplantation》2012,12(9):2546-2553
Antibody mediated rejection (AMR) activates the classical complement pathway and can be detrimental to graft survival. AMR can be accompanied by thrombotic microangiopathy (TMA). Eculizumab, a monoclonal C5 antibody prevents induction of the terminal complement cascade (TCC) and has recently emerged as a therapeutic option for AMR. We present a highly sensitized 13‐year‐old female with end‐stage kidney disease secondary to spina bifida‐associated reflux nephropathy, who developed severe steroid‐, ATG‐ and plasmapheresis‐resistant AMR with TMA 1 week post second kidney transplant despite previous desensitization therapy with immunoglobulin infusions. Eculizumab rescue therapy resulted in a dramatic improvement in biochemical (C3; creatinine) and hematological (platelets) parameters within 6 days. The patient was proven to be deficient in complement Factor H‐related protein 3/1 (CFHR3/1), a plasma protein that regulates the complement cascade at the level of C5 conversion and has been involved in the pathogenesis of atypical hemolytic uremic syndrome caused by CFH autoantibodies (DEAP‐HUS). CFHR1 deficiency may have worsened the severe clinical progression of AMR and possibly contributed to the development of donor‐specific antibodies. Thus, screening for CFHR3/1 deficiency should be considered in patients with severe AMR associated with TMA. 相似文献
102.
Andreas Schröder Eva OernboelRasmus W. Licht Michael SharpePer Fink 《Journal of clinical epidemiology》2012,65(1):30-41
Objective
This study aimed to test the validity of the 36-item Short-Form Health Survey (SF-36) scales and summaries in patients with severe functional somatic syndromes (FSS), such as fibromyalgia and irritable bowel syndrome.Study Design and Setting
One hundred twenty patients with severe FSS enrolled in a randomized controlled trial filled in the SF-36 questionnaire. We tested for data quality, central scaling assumptions, and agreement with the conceptual model.Results
Most SF-36 scales were found to be valid; however, three scales (role physical, role emotional, and general health) did not satisfy predefined criteria for construct validity, internal consistency, or targeting to the sample. The correlations between SF-36 scales differed considerably from those reported in the general population. As a consequence, the SF-36 summaries, physical component summary (PCS) and mental component summary (MCS), did not accurately reflect their underlying scales and were negatively correlated (r = −0.46, 95% CI [−0.60 to −0.31]).Conclusion
Although the SF-36 is a valuable instrument to assess perceived health in patients with severe FSS, there are problems with some of the scales and with the scoring procedure of the summaries. The SF-36 PCS may, therefore, not accurately measure the physical health status of these patients. Alternative summary measures are needed. 相似文献103.
In vitro evaluation of prothrombin complex concentrates in a thrombin generation assay, using DAPA and purified components of the prothrombinase complex, demonstrated significant levels of coagulant- active "phospholipid replacing" activity. Quantification of this activity showed a significant correlation (r = 0.8747, p less than 0.01) with thrombogenicity measured in vivo in a stasis model in rabbits. Extracted lipid material retained full phospholipid replacing activity in the vitro assay. Thin-layer chromatographic characterization confirmed the presence of phospholipids with known coagulant activity in vitro. In vivo, the extracted material was nonthrombogenic but augmented the thrombogenicity of purified factor Xa. Substitution of a synthetic coagulant-active phospholipid (phosphatidylcholine-phosphatidylserine lipid vesicles) for the extracted phospholipid produced a similar augmentation of a factor-Xa- induced thrombogenicity in vivo. It is concluded that the coagulant- active phospholipid content of prothrombin complex concentrates is a major determinant of thrombogenicity but requires the presence of activated clotting factors for its expression in vivo. 相似文献
104.
Paul Licht Susan Walker Farmer Harold Papkoff 《General and comparative endocrinology》1978,35(3):289-294
Recombinations among the α- and β-subunits of luteinizing hormone (LH) from a mammal (sheep) and a turtle (Chelonia mydas) were tested in a variety of bioassays and binding assays to study the role of the two subunits in “species specificity” of hormone function. The subunits alone were relatively inactive, and a high degree of activity was regenerated when the two homologous pairs of α- and β-subunits were combined. Both intact molecules and homologous recombinations were active in the Xenopus ovulation assay, and the hybrids formed with turtle and ovine subunits were essentially as potent as the two intact native molecules in this assay. Turtle LH was inactive in a rat Leydig cell testosterone bioassay and in several LH binding tests with rat gonadal tissues. Only the subunit recombinations containing ovine LHβ showed appreciable activity in these tests; the hybrid containing turtle LHα and ovine LHβ was considerably more active than the individual constituents, but it was still much less active than the homologous ovine combination in the rat Leydig cell assay. Thus, while the turtle LHα is capable of combining with ovine LHβ, it may not be able to substitute fully for ovine LHα. In contrast, ovine LH was essentially inactive in bioassays and binding assays with turtle gonadal tissues, and only subunit recombinations containing turtle LHβ were active in these tests: the hybrid between ovine LHα and turtle LHβ showed essentially full activity. These results indicate that the β-subunit is primarily responsible for determining species specificity in responses to LH. 相似文献
105.
Drug-induced thrombocytopenia is associated with increased binding of IgG to platelets both in vivo and in vitro 总被引:3,自引:0,他引:3
Kelton JG; Meltzer D; Moore J; Giles AR; Wilson WE; Barr R; Hirsh J; Neame PB; Powers PJ; Walker I; Bianchi F; Carter CJ 《Blood》1981,58(3):524-529
Thrombocytopenia is a common serious adverse effect of drug treatment. A variety of in vitro diagnostic techniques to confirm the diagnosis are available, but the majority lack sufficient sensitivity to detect all cases of drug-induced thrombocytopenia. We studied 19 patients with suspected drug-induced thrombocytopenia and demonstrated that platelet- associated IgG (PAIgG) was elevated in all at the time of thrombocytopenia, and PAIgG returned to normal levels as the thrombocytopenia resolved. In the majority of patients, the platelet count rapidly returned to normal after the drug was discontinued; however, in six patients, the thrombocytopenia persisted well beyond the period of time that the offending drug would be expected to be cleared from the blood. In 13 patients, serum obtained after recovery was used to identify the drug responsible for the thrombocytopenia in an in vitro assay. In all cases, the addition of the drug historically associated with the thrombocytopenic episode was associated with an increased binding of IgG to control platelets. For uncertain reasons, the concentration of drug required to increase the in vitro binding of IgG to test platelets was often more than the concentration usually achieved in vivo. Wider application of these techniques may provide better understanding of the clinical characteristics and mechanisms responsible for drug-induce thrombocytopenia. 相似文献
106.
107.
Gonadotropin preparations from three classes of tetrapods (amphibian, avian, and mammalian) and a chondrosteian and teleost fish were used to investigate the species specificity and hormonal (FSH/LH) specificity of in vitro steroid (estradiol-17 beta) production by the teleost ovary. Results for ovaries from one species of gobiid, Gillichthys mirabilis, and two cichlids, Cichlasoma citrinellum and Sarotherodon mossambicus, revealed a general lack of species specificity in the response to tetrapod gonadotropins, but the piscine, especially sturgeon, gonadotropins were much more potent than any of the tetrapod hormones. All three species of teleost ovaries responded to both types of tetrapod gonadotropins (FSH and LH), but the extent of hormonal specificity was variable. The gobiid ovary showed the highest LH specificity (potencies of FSHs = 7-14% of LH); in the two cichlids the potency of FSHs ranged from 11 to 100% of the respective LHs. In general, the specificity of the ovarian steroidogenic response to gonadotropins parallels that observed for testosterone secretion in the males of the same three fish, but the differential actions of the tetrapod hormones (both species and hormonal specificity) are more exaggerated for the testes. 相似文献
108.
Previous observations from our laboratory have shown that equine LH can suppress the FSH induced cyclic AMP production in rat seminiferous tubule cells in vitro. The present investigation was carried out to determine the effect of various subunits in this system. The ratios (w/w) of subunits to equine FSH tested was 1:3, 3:1 and 30:1 with a standard dose of 0.3 microgram of the FSH. It was noted that equine LH-beta was not effective up to a 10 microgram concentration in inhibiting the cyclic AMP production induced by equine FSH. Under these conditions, equine LH-alpha suppressed the FSH activity in a dose dependent manner. However, alpha subunits derived from several other species of LH were without any effect on FSH action. Histidine modified derivative of equine LH and its alpha subunit, both of which lack biological activity in the rat Leydig cell assay for LH, were found to be inactive as inhibitors of the equine FSH response. Thus, these results show that the suppressive effect of equine LH on FSH action in the rat seminiferous tubule is a function of the equine LH alpha subunit. 相似文献
109.
110.