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131.
The development of an immune response towards factor VIII (FVIII) remains the major complication of haemophilia A replacement therapy. Product-related risk factors have recently been identified on the basis of epidemiological studies, but the mechanism is not understood. To this end, various commercially available FVIII concentrates were administered by the IV route to FVIII-knockout mice and the resulting immune response was characterised. Significantly higher inhibitor titres (Bethesda assay) were observed for one recombinant FVIII and one plasma-derived FVIII product depleted in von Willebrand factor (VWF). Inhibitor titres were reduced upon pre-incubation of FVIII with purified VWF. Epitope specificity of anti-FVIII IgG was characterised using FVIII-fragments produced in E. coli. Concentrates with no or reduced VWF-level elicited antibodies recognising predominantly the acidic a1 and a3 regions. Addition of VWF prior to injection also modified the epitope specificity. FVIII concentrates, therefore, show qualitative and quantitative variations in immunogenicity, which are at least partly modulated by VWF. 相似文献
132.
Monge-Argiles J Maloteaux J Van Den Bergh P Sindic C 《Neurología (Barcelona, Spain)》2002,17(2):110-112
We report a patient with a peripheral neuropathy as the first symptom of sarcoidosis. The systemic illness was proved by the presence of typic granulomes in the bone marrow. The fact that sarcoidosis is the cause for the neuropathy is supported by the temporary relation and by the good response of all clinical picture to the corticosteroid therapy.Sarcoid neuropathy can rarely be the presenting feature of sarcoidosis. 相似文献
133.
Vanzieleghem B Gilles JG Desqueper B Vermylen J Saint-Remy JM 《Thrombosis and haemostasis》2000,83(6):833-839
A Severe Combined Immunodeficient (SCID) mouse model has been established to evaluate experimental conditions leading to the production of factor VIII (FVIII) autoantibodies. To this end, we humanized 10 groups of 7 mice with peripheral blood mononuclear cells of 10 unrelated healthy blood donors (15 x 10(6) cells/mouse). Mice were injected with saline or immunized i.p. with 50 IU of a plasma derived human FVIII 24 h after reconstitution. Further immunization was made with 25 IU of FVIII every fortnight during 6 weeks and animals were sacrificed after 8 weeks. All reconstituted mice showed a spontaneous production of anti-FVIII antibodies in the absence of immunization with the corresponding antigen. However, no differences were observed regarding the quantity or the quality of these antibodies produced in the immunized or the saline group, indicating that tolerance to FVIII had been transferred with cell reconstitution. Affinity purified FVIII specific antibodies were capable of inhibiting FVIII activity and preventing the binding of FVIII to phospholipids in a dose-dependent manner. Immunoprecipitation experiments showed that the antibodies recognized only the C1 and C2 light chain domains. Since antibodies of interest can be found in the SCID mouse model and, moreover, since they are qualitatively comparable with the source donor's antibodies, this model provides a tool to study the regulation of tolerance against self antigens in normal subjects and in acquired haemophilia patients. 相似文献
134.
Hans JM van Grinsven Mary H Ward Nigel Benjamin Theo M de Kok 《Environmental health : a global access science source》2006,5(1):26-6
Several authors have suggested that it is safe to raise the health standard for nitrate in drinking water, and save money
on measures associated with nitrate pollution of drinking water resources. The major argument has been that the epidemiologic
evidence for acute and chronic health effects related to drinking water nitrate at concentrations near the health standard
is inconclusive. With respect to the chronic effects, the argument was motivated by the absence of evidence for adverse health
effects related to ingestion of nitrate from dietary sources. An interdisciplinary discussion of these arguments led to three
important observations. First, there have been only a few well-designed epidemiologic studies that evaluated ingestion of
nitrate in drinking water and risk of specific cancers or adverse reproductive outcomes among potentially susceptible subgroups
likely to have elevated endogenous nitrosation. Positive associations have been observed for some but not all health outcomes
evaluated. Second, the epidemiologic studies of cancer do not support an association between ingestion of dietary nitrate
(vegetables) and an increased risk of cancer, because intake of dietary nitrate is associated with intake of antioxidants
and other beneficial phytochemicals. Third, 2–3 % of the population in Western Europe and the US could be exposed to nitrate
levels in drinking water exceeding the WHO standard of 50 mg/l nitrate, particularly those living in rural areas. The health
losses due to this exposure cannot be estimated. Therefore, we conclude that it is not possible to weigh the costs and benefits
from changing the nitrate standard for drinking water and groundwater resources by considering the potential consequences
for human health and by considering the potential savings due to reduced costs for nitrate removal and prevention of nitrate
pollution. 相似文献
135.
随着禽流感病毒H5N1的不断蔓延,越来越有可能发生人类流感的大流行。如果现在发生流感的大流行,不仅还没有有效的疫苗,而且还可能造成抗病毒药物的缺乏。目前尚没有证据表明抗流感药物神经氨酸酶抑制剂(neuraminidaseinhibitor对)禽流感和流感大流行的病毒有效,给予神经氨酸酶抑制剂后,感染H5N1禽流感病毒的患者的死亡率仍然很高。而且流感病毒的耐药会进一步限制抗病毒药物的疗效。假如继发性细菌感染是流感常见且重要的致命性并发症,那么抗生素在人类流感大流行中将占有重要的一席地位。 相似文献
136.
137.
138.
Janjaap van der Net Patrick van der Torre Raoul HH Engelbert Vivian Engelen Femke van Zon Tim Takken Paul JM Helders 《Pediatric rheumatology online journal》2008,6(1):2
Objective
To describe the level of motor performance and functional skills in young children with JIA. 相似文献139.
Marijke JM Chin A Paw Amika S Singh Johannes Brug Willem van Mechelen 《The international journal of behavioral nutrition and physical activity》2008,5(1):41
Objectives
This paper aims to identify the mediating mechanisms of a school-based obesity prevention program (DOiT). 相似文献140.