Transfection-based genomic readout for identifying rare transcriptional splice variants.

Understanding the transcriptome, defined as the complete transcriptional component of the genome, is far more complex than originally considered. Even with the near fully resolved human and mouse genomes, for which extensive databases of transcribed sequence data (e.g.

Construction, expression, and purification of chimeric protein reagents based on immunoglobulin fc regions.

Recombinant fusion proteins incorporating experimental protein domains fused to immunoglobulin Fc regions have become widely utilized in studies of protein-ligand interactions. The advantages of these systems include an inherent increase in avidity provided by the multimerization of Fc regions, combined with robust detection methods based on numerous commercially available secondary reagents directed against the Fc tag. We describe a set of methods for subcloning, expression, and purification of chimeric protein reagents containing a protein domain (or domains) of interest fused to a C-terminal moiety derived from the Fc region of either IgG or IgM.

Natriuretic peptides in children: physiology and clinical utility.

Purpose Of Review: This article reviews the genetics, biochemistry, and physiology of the natriuretic polypeptide family and their receptors; their roles in cardiac, bone, and lipid metabolism in children; and pharmacological agents that utilize the natriuretic polypeptide system.

Recent Findings: Clinically, measurements of circulating levels of the natriuretic polypeptides are useful diagnostic and prognostic markers of cardiovascular disease in children. The natriuretic polypeptides also play an important role in growth and body composition.

Blood flow dynamics of one cardiac cycle and relationship to mechanotransduction and trabeculation during heart looping.

Analyses of form-function relationships during heart looping are directly related to technological advances. Recent advances in four-dimensional optical coherence tomography (OCT) permit observations of cardiac dynamics at high-speed acquisition rates and high resolution. Real-time observation of the avian stage 13 looping heart reveals that interactions between the endocardial and myocardial compartments are more complex than previously depicted.

Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency.

Autosomal recessive interleukin-1 receptor-associated kinase (IRAK)-4 and myeloid differentiation factor (MyD)88 deficiencies impair Toll-like receptor (TLR)- and interleukin-1 receptor-mediated immunity. We documented the clinical features and outcome of 48 patients with IRAK-4 deficiency and 12 patients with MyD88 deficiency, from 37 kindreds in 15 countries.The clinical features of IRAK-4 and MyD88 deficiency were indistinguishable.

A role for the cytoskeleton in heart looping.

Over the past 10 years, key genes involved in specification of left-right laterality pathways in the embryo have been defined. The read-out for misexpression of laterality genes is usually the direction of heart looping. The question of how dextral looping direction occurred mechanistically and how the heart tube bends remains unknown.

Tubulointerstitial nephritis induced by the leukotriene receptor antagonist pranlukast.

A 7-year-old boy with asthma was receiving the leukotriene receptor antagonist pranlukast (Ultair; SmithKline Beecham; Pittsburgh) as part of an open-label clinical trial. The patient's asthma improved, and he remained asymptomatic; but routine study evaluations 9 to 12 months into therapy showed microhematuria, proteinuria, glucosuria, anemia, and renal insufficiency. Renal biopsy demonstrated changes classic for acute allergic tubulointerstitial nephritis (ATIN), with mixed interstitial inflammatory infiltrate including eosinophils.