Atopic dermatitis (AD) has been sub-classified into extrinsic and intrinsic types according to the presence or not of allergen-specific IgE antibodies. Although total serum IgE levels are frequently elevated in AD, their potential to predict allergen-specific IgE (asIgE) has rare ly been studied. We investigated 103 children with AD and suspected allergen-specific sensitization. A thorough clinical examination, a structured medical history and total serum IgE and asIgE measurements were performed. Fifty-three male and 50 female patients, median age 35 months (range 3 months to 17 years), were recruited. Sixty-three percent of patients were asIgE positive, while 37% did not reveal such IgE antibodies; median total serum IgE levels were 224.0 kU/l (14-12,013 kU/l) and 25.2 kU/l (0-4352 kU/l), respectively. Associations of asIgE status with atopic co-morbidity and total serum IgE levels were statistically significant. At a cut-off total serum IgE level of 106 kU/l (sensitivity 68.7%; specificity 92.3%), positive and negative predicted values (93.6% and 64.3%, respectively) were determined. Clinical decision points predictive of positive asIgE results were identified in 90%, 95% and 99% of patients, respectively. Total serum IgE values were significantly associated with the asIgE status of investigated patients. However, these preliminary data warrant further large-scale investigations before total serum IgE levels can be regarded as a clinically useful parameter between patients with extrinsic atopic dermatitis and intrinsic atopic dermatitis.

Mutations in the DAX-1 (NR0B1) gene cause the X-linked form of adrenal hypoplasia congenita (AHC), which is constantly found associated with hypogonadotropic hypogonadism (HHG). DAX-1 encodes an atypical orphan member of the nuclear hormone receptor superfamily. DAX-1 acts at multiple levels to repress the expression of genes involved in steroid hormone metabolism through a potent transcriptional repression domain present in its C-terminus, which is similar to the nuclear receptors' ligand binding domain. All DAX-1 mutations causing AHC/HHG alter the protein C-terminal domain, impairing its nuclear localization and, consequently, its transcriptional repression activity. Here we show that DAX-1 AHC mutants have a misfolded conformation, which correlates with their cytoplasmic retention. Extensive structure-function analysis reveals that the chemical nature of amino acid residues at positions interested by AHC mutations and critical determinants in helix 12 affect DAX-1 nuclear localization and transcriptional silencing. Surprisingly, mutations in a conserved putative corepressor binding surface have a negative effect upon DAX-1 transcriptional repression only when they also affect protein expression levels. These data suggest that a folding defect underlies the impaired function of DAX-1 missense mutants found in AHC/HHG patients and that interactions with transcriptional cofactors different from known corepressors mediate DAX-1 silencing properties.

Mutations in the DAX-1 [dosage-sensitive sex reversal-adrenal hypoplasia congenita (AHC) critical region on the X chromosome; NR0B1] gene cause X-linked AHC associated with hypogonadotropic hypogonadism. DAX-1 encodes an unusual orphan member of the nuclear hormone receptor superfamily, acting as a transcriptional repressor of genes involved in the steroidogenic pathway. All DAX-1 mutations found in AHC patients alter the protein C terminus, which shares similarity to the ligand binding domain of nuclear hormone receptors and bears transcriptional repressor activity. This property is invariably impaired in DAX-1 AHC mutants. Here we show that the localization of DAX-1 AHC mutant proteins is drastically shifted toward the cytoplasm, even if their nuclear localization signal, which resides in the N terminal of the protein, is intact. Cytoplasmic localization of DAX-1 AHC mutants correlates with an impairment in their transcriptional repression activity. These results reveal a critical role of an intact C terminus in determining DAX-1 subcellular localization and constitute an important example of a defect in human organogenesis caused by impaired nuclear localization of a transcription factor. A drenal hypoplasia congenita (AHC) is an inherited disorder of the adrenal cortex commonly manifested as an earlyonset adrenal insufficiency syndrome. Two different forms of this disease have been recognized: a X-linked form and a rare autosomal recessive or sporadic form (1). AHC is a lethal disease if untreated, mainly because of mineralocorticoid deficit. Although it can present a wide clinical spectrum (1-3), a constant feature of the X-linked syndrome is the association with hypogonadotropic hypogonadism (HHG). It has been shown that HHG is caused by combined hypothalamic failure in gonadotropin-releasing hormone release and pituitary defect in gonadotropin production (2). Mutations in the DAX-1 (dosagesensitive sex reversal-AHC critical region on the X chromosome gene 1; NR0B1) gene, situated in Xp21, are responsible for the X-linked form of AHC͞HHG (4, 5).DAX-1 encodes an unusual orphan member of the nuclear hormone receptor superfamily (4-7) whose expression is restricted to the adrenal cortex, testis, ovary, pituitary gonadotropes, and hypothalamic ventromedial nucleus (8,9). This pattern of expression closely matches the characteristics of the disease and suggests that DAX-1 also plays a role in reproductive function. Strikingly, inactivation of the mouse Ahch homologue does not produce adrenal hypoplasia, but male sterility caused by progressive testicular seminiferous tubules degeneration (10). Other links with reproductive function and phenotypical sex determination are provided by the findings that the DAX-1 gene lies inside the critical region on the X chromosome whose duplication causes dosage-sensitive sex reversal in XY individuals (11,12), and that overexpression of DAX-1 in particular mouse strains causes phenotypical sex reversal (13). Furthermore, mouse Dax-1 has been shown to antagonize the synergisti...

These data suggest a significant impact of selected miRNA polymorphisms on prognosis in AGC.

Background: Allergic bronchopulmonary aspergillosis

IntroductionContinuous or episodic allergen exposure is a major risk factor of frequent symptoms and exacerbations for patients with allergic asthma. It has been shown that temperature-controlled laminar airflow (TLA) significantly reduced allergen exposure and airway inflammation and improved quality of life of patients with poorly controlled allergic asthma.ObjectiveThe objective was to evaluate the effects of nighttime TLA when used during real-life conditions for 12 consecutive months in addition to the patients’ regular medication.MethodsThis multicenter, pre- and postretrospective observational study included patients with inadequately controlled moderate-to-severe allergic asthma who received add-on treatment with TLA for 12 consecutive months. Data on medication use, asthma control, asthma symptoms, lung function, use of hospital resources, and exacerbations were collected after 4 and 12 months and compared with corresponding data collected retrospectively from medical records during the year prior to inclusion in the study.ResultsData from 30 patients (mean age 28; range 8–70) completing 4 months and 27 patients completing 12 months of TLA use are presented. The mean number of exacerbations was reduced from 3.6 to 1.3 (p<0.0001), and the ratio of asthma-related emergency room visits or hospitalizations diminished from 72.4 to 23.3% (p=0.001) or from 44.8 to 20.0% (p<0.05), respectively, after 12 months of TLA use. The Asthma Control Test index increased from 14.1 to 18.5 (p<0.0001). After 4 months of TLA use, clear improvements can be shown for most variables in line with the data collected after 12 months.ConclusionsThe addition of TLA to the patients’ regular medication significantly reduced exacerbations, asthma symptoms, and the utilization of hospital resources. The data support that TLA may be an important new non-pharmacological approach in the management of poorly controlled allergic asthma.

EIT changes during forced expiration correlate with lung function parameters, clinical findings, and radiology. Regional analysis of EIT illustrates regional lung function and visualizes individual therapeutic effects. Pediatr Pulmonol. 2016;51:1191-1199. © 2016 Wiley Periodicals, Inc.

Global FV loops derived from EIT correlate well with spirometry. Positive bronchospasmolysis can be observed in EIT-derived FV loops. Flow-volume loops originated from EIT have a potential to visualize pulmonary function.