The intermediate filament cytoskeleton of corneal epithelial cells is composed of cornea-specific keratins K3 and K12 (refs 1,2). Meesmann's corneal dystrophy (MCD) is an autosomal dominant disorder ...causing fragility of the anterior corneal epithelium, where K3 and K12 are specifically expressed. We postulated that dominant-negative mutations in these keratins might be the cause of MCD. K3 was mapped to the type-II keratin gene cluster on 12q; and K12 to the type-I keratin cluster on 17q using radiation hybrids. We obtained linkage to the K12 locus in Meesmann's original German kindred (Zmax = 7.53; theta = 0) and we also showed that the phenotype segregated with either the K12 or the K3 locus in two Northern Irish pedigrees. Heterozygous missense mutations in K3 (E509K) and in K12 (V143L; R135T) completely co-segregated with MCD in the families and were not found in 100 normal unrelated chromosomes. All mutations occur in the highly conserved keratin helix boundary motifs, where dominant mutations in other keratins have been found to severely compromise cytoskeletal function, leading to keratinocyte fragility phenotypes. Our results demonstrate for the first time the molecular basis of Meesmann's corneal dystrophy.
This study investigated longitudinally the extent to which childhood friends who smoke influence adolescents' smoking transitions, and compared that influence with that of parents who smoke. In a ...sample of 4744 children, results showed that the probability, per close friend, that a smoking close friend influenced the adolescent to make the first transition to trying smoking was 38% (95% CI: 28%, 46%); to make the second transition from trying to monthly smoking, 10% (95% CI: 5%, 15%); and to make the third transition from monthly to daily smoking, 11% (95% CI: 5%, 17%). Compared to parents' smoking, close friends' smoking was 12% (
p
=
0.03)
more influential for the
first transition,
no different for the
second transition (
p
=
0.53), and 16% (
p
=
0.01)
less influential for the
third transition. Results provide
new evidence suggesting that childhood close friends who smoke influence not only
initiation but also
escalation of adolescents' smoking. Results also confirmed the important role of parents' smoking. Targeting
both childhood close friends' and parents' smoking would be valuable in prevention research.
The first prospective investigation of the extent to which parental smoking cessation predicts their children's daily smoking.
Parental smoking status was assessed when children were aged 8/9 years ...and children's smoking status was assessed at age 17/18 years.
Twenty Washington State school districts in the control group of the Hutchinson Smoking Prevention Project.
Questionnaire data were gathered on 3012 children (49% female and 91% Caucasian) and both of their parents in a cohort with a 95% retention rate.
When both parents quit smoking, children's odds of daily smoking were reduced by 39% (95% CI = 15%,56%) compared to when both parents were current smokers.Furthermore, when both parents never smoked then children's odds of daily smoking were reduced by 71% (95% CI = 62%,78%).
Parental smoking cessation is associated with reduced risk of their children's daily smoking. Parents who quit still place children at substantially higher risk compared to parents who never smoked.