The role of schlafen in macrophages and inflammation

Macrophages are essential for host defence, but when excessively and persistently activated, these cells contribute to the initiation and progression of inflammatory diseases such as rheumatoid arthritis. Investigating the function of inflammatory genes in macrophages may identify novel therapeutic targets for inflammatory diseases. One family of transcripts that are highly expressed in activated macrophages are members of the Schlafen (Slfn) gene family; a recently identified family whose function is still unknown. This study examined the mRNA expression of Slfn in activated bone marrowderived macrophages in vitro, and in collagen-induced arthritis (CIA) in vivo. Real-time PCR expression analyses of bone marrow-derived macrophages stimulated with lipopolysaccharide (LPS) over a time course, revealed differential expression of individual Slfn family genes. In particular, Slfn-1, Slfn-2, and Slfn-4 were maximally induced after 24 hours. The maximal induction of Slfn-8 and Slfn-9 was observed after 4 hours of LPS treatment. Individual members of the Slfn family were also differentially expressed in CIA, a model of rheumatoid arthritis. mRNA levels of Slfn-1, Slfn-2, Slfn-4 and Slfn-5 were elevated in joints affected by CIA. To investigate the role of Slfn-4, we have generated a transgenic mouse line, which over expresses Slfn-4 specifically in cells of the mononuclear phagocyte system, by using a novel binary expression based on the c-fms promoter and Gal4. Further characterisation of the Slfn-4 over expressing mouse line will be used to assess the function of Slfn-4 in macrophage biology and inflammation, and its potential as a therapeutic target

Further delineation of the DFNA5 phenotype: Results of speech recognition tests

Speech recognition scores were analyzed in 34 carriers of a DFNA5 mutation. Cross-sectional linear regression analysis (last visit, maximum recognition score in %Correct on age or PTA(1,2,4 kHz)) established onset age (score 90%) at 16 years and onset PTA(1,2,4 kHz) level (score 90%) at 41 dB hearing level. The deterioration rate was 0.7%/y in the plot of maximum score against age, whereas the deterioration gradient was 0.4%/dB in the plot of maximum score against PTA(1,2.4 kHz). Given the previously demonstrated rapid progression of hearing impairment, speech recognition was relatively good: at age 70, the score was still >50%

Nonsyndromic hearing impairment is associated with a mutation in DFNA5.

Nonsyndromic hearing impairment is one of the most heterogeneous hereditary conditions, with more than 40 loci mapped on the human genome, however, only a limited number of genes implicated in hearing loss have been identified. We previously reported linkage to chromosome 7p15 for autosomal dominant hearing impairment segregating in an extended Dutch family (DFNA5). Here, we report a further refinement of the DFNA5 candidate region and the isolation of a gene from this region that is expressed in the cochlea. In intron 7 of this gene, we identified an insertion/deletion mutation that does not affect intron-exon boundaries, but deletes five G-triplets at the 3' end of the intron. The mutation co-segregated with deafness in the family and causes skipping of exon 8, resulting in premature termination of the open reading frame. As no physiological function could be assigned, the gene was designated DFNA5

Evaluation of phenoxymethylpenicillin treatment of acute otitis media in children aged 2–16

Objective. To study the clinical recovery from acute otitis media ( AOM) in children, 2-16 years of age, managed with or without treatment with phenoxymethylpenicillin ( PcV). Design. An open, prospective randomized trial. Children aged between 2 and 16 years, presenting with one- or double-sided AOM ( without perforation) with symptom duration of less than four days, were included. The children were randomized to PcV for five days or to no primary antibiotic treatment. A health score and compliance were registered on a daily basis for seven days. Setting. A total of 32 health centres and 72 GPs in south-east Sweden. Subjects. Children aged 2-16 presenting with earache. Main outcome measures. Recovery time, symptom duration, frequency of complications ( up to three months) and consumption of healthcare services independent of treatment with or without antibiotics. Results. A total of 179 patients carried out the trial; 92 were randomized to PcV, 87 to no primary antibiotic treatment. The median recovery time was four days in both groups. Patients who received PcV had less pain ( p<0.001) and used fewer analgesics. There were no significant differences in the number of middle-ear effusions or perforations at the final control after three months. Children randomized to PcV treatment consulted less ( p<0.001) during the first seven days. Conclusions. Our investigation supports that PcV treatment of AOM does not affect the recovery time or complication rates. PcV provided some symptomatic benefit in the treatment of AOM in otherwise healthy children, aged 2-16 years