Immunoglobulin E (IgE) is central to the induction of allergic diseases through its binding to the high-affinity receptor (Fc epsilon R1) on mast cells and basophils. Crosslinking by allergens of the bound IgE leads to the release of various inflammatory mediators. IgE production by B cells requires a physical interaction with T cells, involving a number of surface adhesion molecules, as well as the soluble factors interleukin-4 (IL-4) and IL-13 (ref. 5) produced by T cells, basophils and mast cells. Here we report that, in the presence of IL-4, mast and basophilic cell lines can provide the cell contact signals that are required for IgE synthesis. The human cell lines HMC-1 (mast) and KU812 (basophilic) both express the ligand for CD40 (CD40L) which is shown to be responsible for the IgE production. Moreover, freshly isolated purified human lung mast cells and blood basophils are also shown to express CD40L and to induce IgE production. This evidence suggests that mast cells and basophils may therefore play a key role in allergy not only by producing inflammatory mediators, but also by directly regulating IgE production independently of T cells.

Multiple sclerosis is a chronic demyelinating disease of the central nervous system. Spontaneous remyelination during early disease stages is thought to preserve and partially restore function. However, this process ceases in later stages despite the presence of pre-oligodendrocytes. Cuprizone-induced demyelination is a useful model with which to study the remyelination process. Previous studies have demonstrated heterogeneities in demyelination in individual animals. Here we investigated regional differences in demyelination and remyelination within the corpus callosum. C57BL/6 mice were fed 0.2% cuprizone for 5 weeks to induce demyelination. Remyelination was examined 2–5 weeks after cuprizone withdrawal. Immunohistochemistry and electron microscopy were used to quantify regional differences in demyelination, gliosis, and remyelination. We found that, while demyelination was limited in the rostral region of corpus callosum, nearly complete demyelination occurred in the caudal callosum, beginning at approximately −0.5 mm from bregma. Astrogliosis and microgliosis were correlated with demyelination and differed between the rostral and caudal callosal structures. Remyelination upon cessation of cuprizone ensued at different rates with splenium remyelinating faster than dorsal hippocampal commissure. Our data show anatomical differences of cuprizone-induced demyelination and remyelination in the corpus callosum and the importance of examining specific callosal regions in myelin repair studies using this model.

The structure suggests that most of the hyper-IgM syndrome mutations affect the folding and stability of the molecule rather than the CD40-binding site directly. Despite the fact that the hyper-IgM syndrome mutations are dispersed in the primary sequence, a large fraction of them are clustered in space in the vicinity of a surface loop, close to the predicted CD40-binding site.

A method is presented for the rapid determination of substrate selection in a manner that is not restricted to conditions of metabolic and isotopic steady state. Competition between several substrates can be assessed directly and continuously in a single experiment, allowing the effect of interventions to be studied. It is shown that a single proton-decoupled 13C NMR spectrum of glutamate provides a direct measure of the contribution of exogenous 13C-labeled substrates to acetyl-CoA without measurement of oxygen consumption and that steady-state conditions need not apply. Two sets of experiments were performed: one in which a metabolic steady state but a non-steady-state 13C distribution was achieved and another in which both metabolism and labeling were not at steady state. In the first group, isolated rat hearts were supplied with [1,2-13C]acetate, [3-13C]lactate, and unlabeled glucose. 13C NMR spectra of extracts from hearts perfused under identical conditions for 5 or 30 min were compared. In spite of significant differences in the spectra, the measured contributions of acetate, lactate, and unlabeled sources to acetyl-CoA were the same. In the second set of experiments, the same group of labeled substrates was used in a regional ischemia model in isolated rabbit hearts to show regional differences in substrate utilization under both metabolic and isotopic non steady state. This sensitive probe of substrate selection was also demonstrated in intact hearts where excellent time resolution (3 min) of substrate selection was feasible.(ABSTRACT TRUNCATED AT 250 WORDS)

The Federal Reserve Board's triennial Survey of Consumer Finances (SCF) collects information about family incomes, net worth, balance sheet components, credit use, and other financial outcomes. 1 The 2016 SCF reveals broad-based gains in income and net worth since the previous time the survey was conducted, in 2013. 2 During the three years between the beginning of the 2013 and 2016 surveys, real gross domestic product grew at an annual rate of 2.2 percent, the civilian unemployment rate fell from 7.5 percent to 5 percent, and the annual rate of change in the consumer price index averaged 0.8 percent. 3 These changes in aggregate economic performance led to broadbased income gains across many different types of families. Several observations from the SCF about family incomes stand out: 4 ‰ Between 2013 and 2016, median family income grew 10 percent, and mean family income grew 14 percent (figure 1). ‰ Families throughout the income distribution experienced gains in average real incomes between 2013 and 2016, reversing the trend from 2010 to 2013, when real incomes fell or remained stagnant for all but the top of the income distribution. ‰ Families at the top of the income distribution saw larger gains in income between 2013 and 2016 than other families, consistent with widening income inequality. ‰ Families without a high school diploma and nonwhite and Hispanic families experienced larger proportional gains in incomes than other families between 2013 and 2016, although more-educated families and white non-Hispanic families continue to have higher incomes than other families. The improvements in economic activity along with rising house and corporate equity prices combined to support increases in average and median family net worth (wealth) between 2013 and 2016 after both measures remained stagnant between 2010 and 2013. The national CoreLogic Home Price Index increased at an annual rate of 6.5 percent between 1 See box 1, "The Data Used in This Article," for a general description of the SCF data. The appendix to this article provides a summary of key technical aspects of the survey. 2 For a detailed discussion of the 2013 survey as well as references to earlier surveys, see