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Articles by S Tran
Total Records ( 2 ) for S Tran
  P Lamba , J Fortin , S Tran , Y Wang and D. J. Bernard

Selective synthesis and release of FSH from pituitary gonadotropes is regulated by activins. Activins directly stimulate murine FSHβ (Fshb) subunit gene transcription through a consensus 8-bp Sma- and Mad-related protein-binding element (SBE) in the proximal promoter. In contrast, the human FSHB promoter is relatively insensitive to the direct effects of activins and lacks this SBE. The proximal porcine Fshb promoter, which is highly conserved with human, similarly lacks the 8-bp SBE, but is nonetheless highly sensitive to activins. We used a comparative approach to determine mechanisms mediating differential activin induction of human, porcine, and murine Fshb/FSHB promoters. We mapped an activin response element in the proximal porcine promoter and identified interspecies variation in a single base pair in close proximity that conferred strong binding of the forkhead transcription factor FOXL2 to the porcine, but not human or murine, promoters. Introduction of the human base pair into the porcine promoter abolished FOXL2 binding and activin A induction. FOXL2 conferred activin A induction to the porcine promoter in heterologous cells, whereas knockdown of the endogenous protein in gonadotropes inhibited the activin A response. The murine Fshb promoter lacks the high-affinity FOXL2-binding site, but its activin induction is FOXL2 sensitive. We identified a more proximal FOXL2-binding element in the murine promoter, which is conserved across species. Mutation of this site attenuated activin A induction of both the porcine and murine promoters. Collectively, the data indicate a novel role for FOXL2 in activin A-regulated Fshb transcription.

  S Tran , H Francis , J Hoyle and R. Niven

Background Occupational disease linked to the paper recycling industry has not been well documented. No previously confirmed formal diagnosis of occupational asthma (OA) caused by hydroxylamine has been made.

Methods We have assessed and performed occupational assessment of eight workers involved in this industry. Two of these were later diagnosed with OA and are reported here.

Results Both workers developed their respiratory symptoms within 2 years of the first use of the chemical hydroxylamine as part of the ‘de-inking’ process. Hydroxylamine was used as a substitute for glutaraldehyde on risk grounds, although no prior cases of OA had been found. The two workers had worked at the same plant for 11 and 20 years, respectively. Both gave histories of work-related wheeze, shortness of breath and cough. Both cases performed OASYS peak flow records over a 3-week period and had OASYS II index of 2.85 and 2.67, respectively. Both were redeployed on site to non-exposed areas and subsequently demonstrated improvement in bronchial reactivity. Case 2 subsequently consented to and underwent a blinded, placebo-controlled occupational challenge using hydroxylamine demonstrating a significant isolated late asthmatic response.

Conclusions We believe that these are the first two confirmed cases of OA caused by hydroxylamine in the paper recycling industry.

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