(Am J Obstet Gynecol. 2016; 215(2):239.e1–239.e5)Posterior reversible encephalopathy syndrome (PRES) has been reported numerous times in patients with eclampsia, but has also been occasionally ...reported in patients with preeclampsia. PRES is a syndrome in which the affected patients are observed to have reversible vasogenic brain edema in addition to acute neurological symptoms such as seizures, impaired consciousness, and visual disturbances. The purpose of this study was to assess the incidence of PRES in patients with preeclampsia and eclampsia and establish any pathophysiological backgrounds they may share through a comparison of clinical and radiologic characteristics.
The p110δ subunit of class IA PI3K modulates signaling in innate immune cells. We previously demonstrated that mice harboring a kinase-dead p110δ subunit (p110δ(KD)) develop spontaneous colitis. ...Macrophages contributed to the Th1/Th17 cytokine bias in p110δ(KD) mice through increased IL-12 and IL-23 expression. In this study, we show that the enteric microbiota is required for colitis development in germfree p110δ(KD) mice. Colonic tissue and macrophages from p110δ(KD) mice produce significantly less IL-10 compared with wild-type mice. p110δ(KD) APCs cocultured with naive CD4+ Ag-specific T cells also produce significantly less IL-10 and induce more IFN-γ- and IL-17A-producing CD4+ T cells compared with wild-type APCs. Illustrating the importance of APC-T cell interactions in colitis pathogenesis in vivo, Rag1(-/-)/p110δ(KD) mice develop mild colonic inflammation and produced more colonic IL-12p40 compared with Rag1(-/-) mice. However, CD4+ CD45RB(high/low) T cell Rag1(-/-)/p110δ(KD) recipient mice develop severe colitis with increased percentages of IFN-γ- and IL-17A-producing lamina propria CD3+D4+ T cells compared with Rag1(-/-) recipient mice. Intestinal tissue samples from patients with Crohn's disease reveal significantly lower expression of PIK3CD compared with intestinal samples from non-inflammatory bowel disease control subjects (p < 0.05). PIK3CD expression inversely correlates with the ratio of IL12B:IL10 expression. In conclusion, the PI3K subunit p110δ controls homeostatic APC-T cell interactions by altering the balance between IL-10 and IL-12/23. Defects in p110δ expression and/or function may underlie the pathogenesis of human inflammatory bowel disease and lead to new therapeutic strategies.
The human intestinal type IIb Na+-P(i) cotransporter (hNaPi-IIb) gene promoter lacks a TATA box and has a high GC content in the 5'-flanking region. To understand the mechanism of hNaPi-IIb gene ...transcription, the current study was performed to characterize the minimal promoter region and transcriptional factor(s) necessary to activate gene expression in human intestinal cells (Caco-2). With the use of progressively shorter promoter constructs, a minimal promoter extending from bp -58 to +15 was identified and shown to direct high levels of hNaPi-IIb cotransporter expression in Caco-2 cells. Gel mobility shift assays (GMSAs) indicated that two regions could be bound by nuclear proteins from Caco-2 cells: region A at bp -26/-23 and region B at bp -44/-35. The introduction of mutations in region A abolished promoter activity, whereas mutations in region B had no effect. Deletion mutants of the same regions showed identical results. Furthermore, DNase I footprinting experiments confirmed the observation made by GMSAs. Additional studies, which used a specific nuclear factor 1 (NF1) antiserum, demonstrated that NF1 protein(s) binds to the minimal promoter at region A. These results indicated that the NF1 protein(s) is required to activate the basal transcription of hNaPi-IIb gene under normal growth conditions. This study has thus identified a new target gene in the small intestinal epithelium that is directly regulated by NF1 transcriptional factor(s).
Background & Aims Innate immune responses are crucial for host defense against pathogens but need to be tightly regulated to prevent chronic inflammation. Initial characterization of mice with a ...targeted inactivating mutation in the p110δ subunit of phosphoinositide 3-kinase (PI3K p110δD910A/D910A ) revealed defects in B- and T-cell signaling and chronic colitis. Here, we further characterize features of inflammatory bowel diseases in these mice and investigate underlying innate immune defects. Methods Colons and macrophages from PI3K p110δD910A/D910A mice were evaluated for colonic inflammation and innate immune dysfunction. Colonic p110δ messenger RNA expression was examined in interleukin (IL)-10−/− and wild-type germ-free mice during transition to a conventional microbiota. To assess polygenic impact on development of colitis, p110δD910A/D910A mice were backcrossed to IL-10−/− mice. Results A mild spontaneous colitis was shown in PI3K p110δD910A/D910A mice at 8 weeks, with inflammation increasing with age. An inflammatory mucosal and systemic cytokine profile was characterized by expression of IL-12/23. In PI3K p110δD910A/D910A macrophages, augmented toll-like receptor signaling and defective bactericidal activity were observed. Consistent with an important homeostatic role for PI3K p110δ, wild-type mice raised in a germ-free environment markedly up-regulated colonic PI3K p110δ expression with the introduction of the enteric microbiota; however, colitis-prone IL-10−/− mice did not. Moreover, PI3K p110δD910A/D910A mice crossed to IL-10−/− mice developed severe colitis at an early age. Conclusions This study describes a novel model of experimental colitis that highlights the importance of PI3K p110δ in maintaining mucosal homeostasis and could provide insight into the pathogenesis of human inflammatory bowel disease.
Uno Koji, a literary figure of the first rank in twentieth-century Japan, was a maverick who defied literary conventions by combining the playfulness and stylistic verve of pre-Meiji literature with ...the often tortured self-reflection of modern fiction. Elaine Gerbert's startlingly evocative and graceful translation is preceded by an interpretive introduction that places Uno's writing in critical perspective. Here at last is a translation that makes accessible for the first time in English two of the most representative works of this acute, eccentric, and always entertaining author, whose versatility and deft control of language earned him a reputation as one of the great stylists of modern Japanese literature.
Recent observations of core-collapse supernovae (SNe) suggest aspherical explosions. Globally, aspherical structures in SN explosions are thought to encode information regarding the underlying ...explosion mechanism. However, the exact explosion geometries from the inner cores to the outer envelopes are poorly understood. Here, we present photometric, spectroscopic, and polarimetric observations of the Type IIP SN 2021yja and discuss its explosion geometry in comparison to those of other Type IIP SNe that show large-scale aspherical structures in their hydrogen envelopes (SNe 2012aw, 2013ej and 2017gmr). During the plateau phase, SNe 2012aw and 2021yja exhibit high continuum polarization characterized by two components with perpendicular polarization angles. This behavior can be interpreted as being due to a bipolar explosion, where the SN ejecta is composed of a polar (energetic) component and an equatorial (bulk) component. In such a bipolar explosion, an aspherical axis created by the polar ejecta would dominate at early phases, while the perpendicular axis along the equatorial ejecta would emerge at late phases after the photosphere in the polar ejecta has receded. Our interpretation of the explosions in SNe 2012aw and 2021yja as bipolar is also supported by other observational properties, including the time evolution of the line velocities and the line shapes in the nebular spectra. The polarization of other Type IIP SNe that show large-scale aspherical structures in the hydrogen envelope (SNe 2013ej and 2017gmr) is also consistent with the bipolar-explosion scenario, although this is not conclusive.
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