Transcriptomic Comparison of Human Peripartum and Dilated Cardiomyopathy Identifies Differences in Key Disease Pathways.

Peripartum cardiomyopathy (PPCM) is a rare form of acute onset heart failure that presents in otherwise healthy pregnant women around the time of delivery. While most of these women respond to early intervention, about 20% progress to end-stage heart failure that symptomatically resembles dilated cardiomyopathy (DCM). In this study, we examined two independent RNAseq datasets from the left ventricle of end-stage PPCM patients and compared gene expression profiles to female DCM and non-failing donors.

Immune cell profile and immune-related gene expression of obese peripheral blood and liver tissue.

Obesity is associated with changes in immune cell subpopulations. However, tissue and blood obesity-responsive immune phenotypic pathways have not been contrasted. Here, the local niche immune cell population and gene expression in fatty liver is compared to peripheral blood of obese individuals.

Tissue resident macrophages are sufficient for demyelination during peripheral nerve myelin induced experimental autoimmune neuritis?

The contribution of resident endoneurial tissue macrophages versus recruited monocyte derived macrophages to demyelination and disease during Experimental Autoimmune Neuritis (EAN) was investigated using passive transfer of peripheral nerve myelin (PNM) specific serum antibodies or adoptive co-transfer of PNM specific T and B cells from EAN donors to leukopenic and normal hosts. Passive transfer of PNM specific serum antibodies or adoptive co-transfer of myelin specific T and B cells into leukopenic recipients resulted in a moderate reduction in nerve conduction block or in the disease severity compared to the normal recipients. This was despite at least a 95% decrease in the number of circulating mononuclear cells during the development of nerve conduction block and disease and a 50% reduction in the number of infiltrating endoneurial macrophages in the nerve lesions of the leukopenic recipients.

Group A Streptococcus Modulates Host Inflammation by Manipulating Polymorphonuclear Leukocyte Cell Death Responses.

Polymorphonuclear leukocyte (PMN) cell death strongly influences the resolution of inflammatory episodes, and may exacerbate adverse pathologies in response to infection. We investigated PMN cell death mechanisms following infection by virulent group A Streptococcus (GAS). Human PMNs were infected in vitro with a clinical, virulent GAS isolate and an avirulent derivative strain, and compared for phagocytosis, the production of reactive oxygen species (ROS), mitochondrial membrane depolarization and apoptotic markers.

Plasmin(ogen) acquisition by group A Streptococcus protects against C3b-mediated neutrophil killing.

The globally significant human pathogen group A Streptococcus (GAS) sequesters the host protease plasmin to the cell surface during invasive disease initiation. Recent evidence has shown that localized plasmin activity prevents opsonization of several bacterial species by key components of the innate immune system in vitro. Here we demonstrate that plasmin at the GAS cell surface resulted in degradation of complement factor C3b, and that plasminogen acquisition is associated with a decrease in C3b opsonization and neutrophil-mediated killing in vitro.

Abnormal myelination in the spinal cord of PTPα-knockout mice.

PTPα interacts with F3/contactin to form a membrane-spanning co-receptor complex to transduce extracellular signals to Fyn tyrosine kinase. As both F3 and Fyn regulate myelination, we investigated a role for PTPα in this process. Here, we report that both oligodendrocytes and neurons express PTPα that evenly distributes along myelinated axons of the spinal cord.

Soluble TNFR1 inhibits the development of experimental autoimmune neuritis by modulating blood-nerve-barrier permeability and inflammation.

The role of TNFalpha/LTalpha during EAN induced by active immunization with peripheral nerve myelin was examined by administering a recombinant soluble chimeric form of human TNF receptor 1 (TNFR1-IgG). TNFalpha and LTalpha do not directly contribute to neurological deficit during EAN since treatment with TNFR1-IgG after onset failed to alter the course of disease. Prophylaxis with a single dose of TNFR1-IgG delayed the onset of EAN and was accompanied initially by inhibition of blood-nerve-barrier permeability and inflammation.

A kinetic model of bone marrow neutrophil production that characterizes late phenotypic maturation.

Acute inflammatory stimuli rapidly mobilize neutrophils from the bone marrow by shortening postmitotic maturation time and releasing younger neutrophils; however, the kinetics of this change in maturation time remains unknown. We propose a kinetic model that examines the rate of change in neutrophil average age at exit from the bone marrow during active mobilization to quantify this response and use this model to examine the temporal profile of late neutrophil phenotypic maturation. Total and CD10(-)/CD16(low) circulating neutrophils were quantified in cardiac surgery patients during extracorporeal circulation (ECC).

Neurophysiological changes in demyelinating and axonal forms of acute experimental autoimmune neuritis in the Lewis rat.

Myelin-sensitized T- and B-cells (lymph node cells) induced experimental autoimmune neuritis (EAN) in Lewis rats after passive transfer to naive recipients. After 6 days, all recipient rats developed tail paresis that progressed to limb paresis within 12-72 h. Progressive nerve conduction changes consistent with demyelination in the sciatic nerve (conduction block and prolongation of the distal motor latencies) and lumbar nerve roots (initial low F-wave frequencies followed by later prolongation in F-wave latencies) were observed during the disease.