Methylation of H19 and its imprinted control region (H19 ICR1) in Müllerian aplasia

Severe hypomethylation of the H19 imprinted control region (ICR1) in two patients with Silver-Russell syndrome (SRS) who have genital malformations has encouraged us to study DNA methylation in a cohort of 83 patients with Müllerian aplasia (MA). Site-specific methylation analyses of H19 ICR1 by quantitative real-time polymerase chain reaction in 80 clinically well-diagnosed Finnish MA patients showed no association between hypomethylation and the MA phenotype, but studies of the H19 locus in 38 patients showed aberrant methylation in 3/16 studied sites.     

MAR, a Novel High-Incidence Rh Antigen Revealing the Existence of an Allelic Sub-System Including Cw (Rh8) and Cx (Rh9) with Exceptional Distribution in the Finnish Population

We present new genetic evidence obtained from population studies on Finns and from the studies on Finnish blood donors as well as their selected families using an antibody that defines a novel high-incidence Rh antigen MAR. Anti-MAR antibody shows an antithetical relationship to both anti-C^w and anti-C^x. The Rh antigens C^w (RH8) and, more strikingly, C^x (RH9) have each an exceptionally high frequency in Finns. Our studies on their genetic relationship indicate that the three antigens C^w, C^x and MAR behave as if being determined by alleles of the same Rh sub-system. Furthermore, we conclude that this sub-system manifests an inheritance pattern that is distinct from but analogous to that of the two well-known allelic sub-systems of C/c and E/e antigens.     

Attempted suicide in mental disorders in young adulthood

Background  

Nationwide general population study establishes the prevalence of suicide attempts in different mental disorders among young adults and their sociodemographic correlates. Current psychiatric symptoms are also examined.     

Timing of puberty and reserve capacity in adolescence as pathways to educational level in adulthood—a longitudinal study

Background: Family socioeconomic status (SES) is related to a child’s educational success. Intermediate pathways for this relationship, such as through pubertal timing and reserve capacity, occur in adolescence.

Aim: To study whether family SES affects a child’s adult education through a psychosocial and behavioural pathway (reserve capacity) and/or a biological pathway (pubertal timing) or only through school achievement in adolescence.

Subjects and methods: Finnish adolescents sampled in five cross-sectional surveys from 1985 to 1995 (n?=?37,876) were followed through the Registry of Completed Education and Degrees until 2009, when they were 29–43?years old. Family SES data also came from this registry. Structural equation modelling adjusted for ages at baseline and follow-up was used.

Results: Low family SES increased the probability of low adult education, delayed pubertal timing (in boys), weak reserve capacity and low school achievement. Reserve capacity and school achievement directly affected adult education and mediated the relationship of family SES with the outcome. Delayed pubertal timing predicted low adult education, except when school achievement was added to the model.

Conclusions: The results show that family SES affects the child’s adult education level through psychosocial and biobehavioural pathways, but the biological pathway is mediated by school achievement.     

Histamine reverses IL-5-afforded human eosinophil survival by inducing apoptosis: pharmacological evidence for a novel mechanism of action of histamine

Eosinophils are essential inflammatory cells in the pathogenesis of asthma and atopic conditions. Histamine, released from mast cells and basophils in response to allergen exposure, is a critical mediator in the allergic response. Histamine exerts its effects via four unequivocally characterized histamine receptors, H(1-4). Several functions of eosinophils have previously been shown to be stimulated by histamine. However, its effects on eosinophil apoptosis are unknown. The aim of the present study was to resolve the effects of histamine on constitutive apoptosis of human eosinophils and on the survival-enhancing action of interleukin (IL)-5. Additional experiments were conducted to elucidate the histamine receptor(s) involved in any response seen and the associated signal transduction cascade. Human isolated peripheral blood eosinophils were cultured in the absence or presence of histamine, IL-5 and receptor antagonists/agonists or mediator inhibitors/analogues. Apoptosis was assessed by measuring the relative DNA content of propidium iodide (PI)-stained cells and the effects were confirmed by morphological analysis with bright field microscopy. Caspase activities were assessed by using commercial Caspase-Glo 3/7, 8 and 9 luminescence assays. Histamine (10-100 microM) partially reversed IL-5-induced human eosinophil survival by enhancing apoptosis as assessed by measuring the relative DNA content of PI-stained cells. This effect was not mediated through any of the known histamine receptors or through non-specific activation of 5-hydroxytryptamine receptors or alpha-adrenoceptors. Moreover, the reversal of IL-5-inhibited eosinophil apoptosis by histamine seemed not to utilize the conventional intracellular second-messenger pathways including cyclic AMP, protein kinase A or phospholipase C. Inhibition of caspase 6 and caspases 1, 10 or 12 reversed the effects of histamine but also inhibited apoptosis in general. In conclusion, the data presented herein indicate that histamine induces human eosinophil apoptosis in the presence of a survival-prolonging cytokine by a mechanism that does not apparently involve the activation of any of the currently known histamine receptor subtypes. The possibility exists that another, as yet unidentified, histamine receptor may exist in human eosinophils that regulates survival, although the participation of histamine receptor-independent mechanisms cannot be excluded.