Glucocorticoid-stimulated,transcription-independent release of annexin A1 by cochlear Hensen cells

Background and purpose:

The current clinical strategy to protect the auditory organ against inflammatory damage by migrating leukocytes is the local delivery of glucocorticoids. However, the mechanism by which glucocorticoids confer this protection remains unknown. Therefore, we investigated the cellular and molecular targets of glucocorticoids in the cochlea that could be involved in preventing leukocyte migration.

Experimental approach:

We used microscopy as well as immunocytochemical and microfluidic techniques to elucidate the effect of dexamethasone, hydrocortisone and prednisolone on the cellular and intracellular distribution of annexin A1 (ANXA1) – a glucocorticoid target known to inhibit leukocyte migration by receptor-mediated signalling – in the cochlea and isolated cochlear cells of guinea pigs.

Key results:

All the cells lining the scala media – the cochlear compartment containing the auditory organ – express ANXA1 and the ANXA1 receptor FPR2/ALX is present in the scala media, as well as in other cochlear ducts. The majority of ANXA1 in the scala media is stored inside lipid droplets within cochlear Hensen cells. Glucocorticoids activate a myosin IIC-mediated mechanism that drives ANXA1 from the lipid droplets to the apical region of the Hensen cells, where ANXA1 is released to the external milieu by a process involving ABC transporters.

Conclusions and implications:

These findings suggest that ANXA1 could be a major mediator of the anti-inflammatory effects of glucocorticoids in the cochlea and identify new molecular targets for prevention of sudden sensorineural hearing loss.     

单亲家庭大学生心理健康状况调查

目的:了解单亲家庭大学生的心理健康状况,并与普通家庭大学生比较。方法:2006-04/05在某医学院校根据学生学号末尾数字随机抽取普通家庭学生345名,其中享受学校减免学费的贫困学生58名,通过查阅学生学籍表的方法获得单亲家庭学生133名,其中享受学校减免学费的贫困学生39名。采用症状自评量表对其心理健康状况进行调查,以量表中各因子均分作为心理健康状况的具体指标,分数越高,表明心理健康状况越差。结果:普通家庭学生有效问卷312份,其中贫困学生有效问卷43份;单亲家庭学生有效问卷104份,其中贫困学生有效问卷32份。①单亲家庭大学生的心理健康状况与普通家庭大学生比较,差异无显著性(P>0.05)。②单亲贫困大学生的强迫和人际敏感因子得分显著低于普通贫困大学生(1.57±0.38,1.87±0.64;1.46±0.41,1.73±0.62,t=2.289,2.265,P<0.05)。③单亲家庭男大学生的强迫、人际敏感和敌对因子得分显著低于普通家庭男大学生(1.50±0.33,1.77±0.47;1.40±0.37,1.63±0.49;1.29±0.34,1.46±0.46,t=2.848,2.750,2.276,P<0.01,0.01,0.05)。单亲家庭女大学生的心理健康状况与普通家庭女大学生比较,差异无显著性(P>0.05)。结论:单亲家庭大学生的心理健康状况与普通家庭总体上并无明显差异。     

2002 Australian Radiology Workforce Report

This paper describes the current status of radiologist provision in Australia, and explores issues relating to its current adequacy, as well as analysing projections of supply and requirements, and their balancing. Data are drawn from several sources including the results of the Royal Australian and New Zealand College of Radiologists Workforce Survey 2000, and the report of the Australian Medical Workforce Advisory Committee Radiology Working Party 2001. The main conclusions to be drawn are that: (i) there is a current shortfall of radiologist supply in Australia; (ii) future requirements (taking all factors into consideration) are expected to grow at a greater rate than projected supply (based on the status quo); and (iii) supply of radiologists should therefore be increased. These conclusions are roughly in line with those from other countries, such as the UK, Canada and USA. Radiologists practising in Australia also appear to have relatively high productivity, including by some international comparisons. These findings are presented in the context of current issues in Australian medical imaging, including provider consolidation and corporatization, globalization and funding.     

A 5-year review of a lympbhoedema service

Data for 714 patients referred during a 5-year period to a specialist lymphoedema service in Oxford, UK, have been recorded on a database. The annual number of new patients almost doubled from 103 to 195. In addition to initial assessments, there were over 1000 follow-up appointments per year. Most patients were seen as out-patients. Fifty-six per cent of the referrals were from Oxfordshire and the rest from further afield. The two largest groups referring patients to the service were general practitioners (43%) and the radiotherapy department (26%). Most referrals were female (84%), and the main cause of lymphoedema was cancer and cancer treatments (68%). After 2 years, only 15% of patients were still attending the clinic regularly. The number of patients receiving intensive treatment increased by almost 40%. These findings emphasize the need to target resources and expertise selectively in order to provide an optimal sericice to patients needing specialist help.     

Site and sequence specific DNA methylation in the neurofibromatosis (NF1) gene includes C5839T: the site of the recurrent substitution mutation in exon 31

CpG dinucleotides provide hotspots for transitional mutations in a variety of genes, some leading to genetic diseases in humans. Although this phenomenon is attributed to cytosine methylation at such sites, direct and specific observations of CpG methylation at the sites of recurrent mutations are lacking. We have used a bisulfite genomic sequencing method to analyze DNA methylation within three representative exons from the neurofibromatosis type 1 (NF1) gene, well recognized for its high frequency of spontaneous mutations. We observed that the cytosine methylation within NF1 exons 28, 29, and 31 is restricted to CpG dinucleotides, including the CpG dinucleotide present at the site of the recurrent NF1 mutation (C5839T; also referred to as R1947X). At several sites, clone-specific methylation differences were also observed. Our results provide experimental evidence for the hypothesis that methylatable CpGs in the NF1 gene contribute to spontaneous germline mutations associated with this gene, by showing that DNA methylation does occur at all CpGs contained within these representative NF1 exons. As well, the DNA methylation seen at the common mutation site in exon 31 may explain why this site is frequently mutated. Methylation-dependent mutagenesis may also provide a basis for some somatic (second hit) mutations which disable the normal allele and result in the development of NF1 associated symptoms.