31 research outputs found
Inhibition of Progenitor Dendritic Cell Maturation by Plasma from Patients with Peripartum Cardiomyopathy: Role in Pregnancy-associated Heart Disease
Dendritic cells (DCs) play dual roles in innate and adaptive immunity based
on their functional maturity, and both innate and adaptive immune responses have
been implicated in myocardial tissue remodeling associated with
cardiomyopathies. Peripartum cardiomyopathy (PPCM) is a rare disorder which
affects women within one month antepartum to five months postpartum. A high
occurrence of PPCM in central Haiti (1 in 300 live births) provided the unique
opportunity to study the relationship of immune activation and DC maturation
to the etiology of this disorder. Plasma samples from two groups (n = 12) of
age- and parity-matched Haitian women with or without evidence of PPCM were
tested for levels of biomarkers of cardiac tissue remodeling and immune
activation. Significantly elevated levels of GM-CSF, endothelin-1, proBNP and
CRP and decreased levels of TGF- were measured in PPCM subjects relative
to controls. Yet despite these findings, in vitro maturation of normal human
cord blood derived progenitor dendritic cells (CBDCs) was significantly
reduced (p < 0.001) in the presence of plasma from PPCM patients relative
to plasma from post-partum control subjects as determined by expression of
CD80, CD86, CD83, CCR7, MHC class II and the ability of these matured CBDCs
to induce allo-responses in PBMCs. These results represent the first findings
linking inhibition of DC maturation to the dysregulation of normal physiologic
cardiac
tissue remodeling during pregnancy and the pathogenesis of PPCM
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Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study
INTRODUCTION: Regional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool.
METHODS: 15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the standardized ENIGMA-VBM tool. Statistical parametric T-maps were generated from each cohort and meta-analyzed to reveal voxel-wise differences between EOP and healthy controls as well as the individual-based association between GM volume and age of onset, chlorpromazine (CPZ) equivalent dose, and other clinical variables.
RESULTS: Compared with healthy controls, individuals with EOP showed widespread lower GM volume encompassing most of the cortex, with the most marked effect in the left median cingulate (Hedges' g = 0.55, p = 0.001 corrected), as well as small clusters of lower white matter (WM), whereas no regional GM or WM volumes were higher in EOP. Lower GM volume in the cerebellum, thalamus and left inferior parietal gyrus was associated with older age of onset. Deficits in GM in the left inferior frontal gyrus, right insula, right precentral gyrus and right superior frontal gyrus were also associated with higher CPZ equivalent doses.
CONCLUSION: EOP is associated with widespread reductions in cortical GM volume, while WM is affected to a smaller extent. GM volume alterations are associated with age of onset and CPZ equivalent dose but these effects are small compared to case-control differences. Mapping anatomical abnormalities in EOP may lead to a better understanding of the role of psychosis in brain development during childhood and adolescence
S.J. Lucas and D.E.R. Fett
Made available by the Northern Territory Library via the Publications (Legal Deposit) Act 2004 (NT).Date:198