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Temmerman ST  Ma CA  Borges L  Kubin M  Liu S  Derry JM  Jain A 《Blood》2006,108(7):2324-2331
Ectodermal dysplasia with immune deficiency (EDI) is caused by alterations in NEMO (nuclear factor [NF]-kappaB essential modulator). Most genetic mutations are located in exon 10 and affect the C-terminal zinc finger domain. However, the biochemical mechanism by which they cause immune dysfunction remains undetermined. In this report, we investigated the effect of a cysteine-to-arginine mutation (C417R) found in the NEMO zinc finger domain on dendritic cell (DC) function. Following CD40 stimulation of DCs prepared from 2 unrelated patients with the NEMO C417R mutation, we found NEMO ubiquitination was absent, and this was associated with preserved RelA but absent c-Rel activity. As a consequence, CD40 stimulated EDI DCs failed to synthesize the c-Rel-dependent cytokine interleukin-12, had impaired up-regulation of costimulatory molecules, and failed to support allogeneic lymphocyte proliferation in vitro. In contrast, EDI DCs stimulated with the TLR4 ligand lipopolysaccharide (LPS) showed normal downstream NF-kappaB activity, DC maturation, and NEMO ubiquitination. These findings show for the first time how mutations in the zinc finger domain of NEMO can lead to pathway specific defects in NEMO ubiquitination and thus immune deficiency.  相似文献   
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Tocolytics were administered in 66 consecutive women in uncomplicated preterm labour with intact fetal membranes (53 singleton and 13 twin pregnancies). C-reactive protein (CRP), a marker of infection, was determined daily and used retrospectively to investigate the role of subclinical infection in preterm labour and to predict the efficacy of tocolysis and the development of a clinical perinatal infection. CRP was also determined in 66 women in uncomplicated labour at term (53 singleton and 13 twin pregnancies). The placenta was examined for histological evidence of infection in all patients who were delivered before 36 weeks (n = 21) and in all women in the control group (n = 66). Elevated CRP levels were more often found in patients who were refractory to tocolysis, suggesting an underlying infectious morbidity. Placental infection was found in 62% of the preterm delivery group and in 12% of the control group. There was an association between elevated CRP levels and histological evidence of placental infection. However, confounding factors such as urinary tract infections limit the usefulness of the CRP test. Because CRP cannot predict clinical perinatal infection accurately, its clinical relevance is very limited.  相似文献   
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Summary A questionnaire study was undertaken among Belgian nurses and physicians with the aim of evaluating whether there is a risk to the health of those persons whose professional life is spent in the operating theatre. Two professional groups occupied in operating theatre were chosen for study; firstly, the membership of the Belgian Society of Anaesthetics and, secondly, operating theatre nurses in Belgium. The control groups chosen for the anaesthetists were the membership of the Belgian Society of Dermatologists and the Belgian Society of Occupational Physicians. The control groups chosen for the operating theatre nurses were nurses working in intensive care units and a small group of social nurses.A total of 1,027 questionnaires was employed for the study and the number of pregnancies studied was 1910. The results did not indicate any statistically significant effects on pregnancy attributable to work in the operating theatre. With the possible exception of more frequent headaches, the health of operating theatre personnel does not seem to have been adversely affected by volatile anaesthetics.  相似文献   
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