Scoring systems for allergies and asthma in clinical research and practice.

Background: Scoring systems are increasingly being developed for various diseases, including asthma and allergic disorders, with the objective of improving the classification of disease severity and the assessment of efficacy of therapeutic modalities. Objective: This review provided concise summaries of published scoring systems used for allergic rhinitis, asthma, atopic dermatitis, urticaria, Stevens-Johnson syndrome/toxic epidermal necrolysis, eosinophilic esophagitis, and systemic allergic reactions (anaphylaxis). Methods: We searched the medical literature between 1985 and 2018 for published scoring systems that have been developed and used in clinical trials or in practice for assessment of asthma and a variety of allergic disorders. Results: The scoring systems for each of these diseases were briefly presented in the text in chronological order of publication, and selected information was presented in the tables for easy comparisons. For more details, the reader should refer to the original relevant publications. Conclusion: Such assessment methods are useful for sound designing of clinical trials, fair comparisons of findings of studies, and objective measurements of patients' progress in clinical practice. The choice of using one scoring system over another would depend on its proven degree of validity, the purpose, and applicability.

Skin rash in a 2-week-old infant.

We presented a case of a male infant with annular patchy rash on his torso since 2 weeks of age. This was initially diagnosed as tinea corporis but did not respond to oral antifungal treatment. Because of the appearance of the rash and a history of a certain disease in a maternal aunt, we suspected the most probable cause of the rash and the diagnosis was confirmed by laboratory testing. Furthermore, laboratory screening of the mother, who was asymptomatic, revealed that she was seropositive for the disease and was counseled on the importance of follow-up. The infant's rash gradually improved and completely disappeared, without any sequalae by 8 months of age.

Repressors NFI and NFY participate in organ-specific regulation of von Willebrand factor promoter activity in transgenic mice.

OBJECTIVE: To determine the role of repressors in cell type and organ-specific activation of von Willebrand factor (VWF) promoter sequences -487 to 247 in vivo. METHODS AND RESULTS: Activation patterns of wild-type and mutant VWF promoters (sequences -487 to 247) containing mutations in repressors nuclear factor-I (NFI)- and nuclear factor Y (NFY)-binding sites were analyzed in transgenic mice. Mutation of the NFI-binding site activated the promoter in heart and lung endothelial cells, whereas mutation of the NFY-binding site activated the promoter in kidney vasculature. Immunofluorescence analyses showed that NFIB was predominant in heart and lung endothelial cells, whereas NFIX was predominantly detected in kidney endothelial cell nuclei. By using chromatin immunoprecipitation, we demonstrated that the distal lung-specific enhancer (containing a YY1 site) of the VWF gene is brought in proximity to the NFI binding site. CONCLUSIONS: The NFI and NFY repressors contribute differentially to organ-specific regulation of the VWF promoter, and the organ-specific action of NFI may reflect its organ-specific isoform distribution. In addition, the lung-specific enhancer region of the endogenous VWF gene may inhibit NFI repressor function through chromatin looping, which can approximate the 2 regions.

Sequences in intron 51 of the von Willebrand factor gene target promoter activation to a subset of lung endothelial cells in transgenic mice.

In vivo analyses of the VWF promoter previously demonstrated that a fragment spanning sequences -487 to +247 targets promoter activation to brain vascular endothelial cells, whereas a longer fragment including 2182 bp of the 5'-flanking sequences, the first exon, and the first intron activated expression in endothelial cells of the heart and muscles as well as the brain of transgenic mice. These results suggested that additional VWF gene sequences were required for expression in other vascular endothelial cells in vivo. We have now identified a region within intron 51 of the VWF gene that is DNase I-hypersensitive (HSS) specifically in non-endothelial cells and interacts with endothelial and non-endothelial specific complexes that contain YY1. We demonstrate that beta-actin is associated with YY1 specifically in the nucleus of non-endothelial cells and is a component of the nuclear protein complexes that interact with the DNase I-hypersensitive region. In vitro transfection analyses demonstrated that HSS sequences containing this YY1-binding site do not significantly affect VWF promoter activity. However, in vivo analyses demonstrated that addition of these sequences to the VWF promoter (-487 to +247) results in promoter activation in lung and brain vascular endothelial cells. These results demonstrate that the HSS sequences in intron 51 of the VWF gene contain cis-acting elements that are necessary for the VWF gene transcription in a subset of lung endothelial cells in vivo.