IL-10-deficient mice exhibit spontaneous enterocolitis and other symptoms akin to Crohn’s disease, indicating that IL-10 might regulate normal physiology in the gut. However, clinical trials with IL-10 in Crohn’s disease were disappointing, although some patients showed healing of intestinal mucosa. This study searched for genetic polymorphisms within the IL-10 pathway. We decided to screen for mutations of the IL-10R1 cDNA in healthy volunteers and Crohn’s disease patients and identified two novel variants: a serine 138-to-glycine (S138G) and a glycine 330-to-arginine (G330R) substitution. The allelic frequency in a European cohort was relatively high (16% for the S138G and 33% for the G330R), and S138G was in strong linkage disequilibrium with G330R. A similar allele frequency was found in a group of Crohn’s patients. In IL-10R1 G330R-expressing monocytes, the inhibitory effect of IL-10 on TNF-α production was diminished, indicating that this variant may be a loss-of-function allele. No such difference was observed between haplotypes 4 (G330R only) and 7 (S138G and G330R). In addition, these IL-10R1 variants had no influence on the IL-10R1 expression density. Structural analysis of the S138G variant revealed that the substitution of S138G may interfere with binding of IL-10 to IL-10R1.
AtUBC2 of Arabidopsis thaliana encodes a structural homolog of the RAD6 gene of Saccharomyces cerevisiae with approximately 65% identical amino acids. Like structural homologs from other organisms, AtUBC2 lacks the carboxyl-terminal extension of mostly acidic amino acids which is present in Rad6p. AtUBC2 was expressed in S. cerevisiae rad6 mutants. It was found to partially complement the UV sensitivity and reduced growth rate of rad6 mutants at elevated temperatures. AtUBC2 however, has no apparent influence on the degradation of N-end rule substrates in the heterologous host.
The increase in arterial-alveolar CO2 difference (D[a-A]CO2) on 100 % O2 breathing was studied in healthy subjects and in chronic bronchitic patients with or without hypoxemia. This increase in D(a-A)CO2 showing the enhancement of the dead-space effect (i. e. of the ventilation/perfusion ratio; VA/Q), resulted from increase in PaCO2 or/and from decrease in PACO2 and was only found in hypoxic bronchitic subjects. In such subjects D(a-A)CO2 increased by about 50 %. This phenomenon seems to arise from the vasomotor effect of pure 02 on pulmonary circulation and the role played by the Haldane effect in increasing PaCO2, and thus D(a-A)CO2 in some subjects is very weak. In subjects where inhalation of pure 02 produced the greatest increase in D(a-A)CO2 and in VA/Q, the calculated value of the venous admixture (Osh/Oτ) after measurement of D(A-a)O2 at the 30th min of hyperoxia was overestimated. Indeed D(A-a) O2 was enlarged by increasing the dead-space effect under 100 % O2 breathing.
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