Tonsil Stromal-Cell Lines Expressing FDC-Like Properties: Isolation, Characterization, and Interaction with B Lymphocytes

The microenvironment of secondary lymphoid organs consists of two major populations of cells, the lymphoid cells and a population of stromal cells that contribute to both tissue architecture and function. Interactions of both populations are essential for the development and control of humoral immune responses. In this study, stromal-cell preparations were obtained by a multistage process. This involved culturing 300-400-μm slices of human tonsil for 6-8 days at 25°C, trypsin digestion of the residual explant, followed by CD45-positive-cell depletion using magnetic beads, and a final period of culture for 4 days to remove remaining nonadherent cells. Phenotypifig with a panel of monoclonal antibodies revealed that the cells express HLA-DR, CD54 (ICAM-1), CD44, but no CD45 nor a range of other markers for epithelial and endothelial cells. Immunoassays of supernatants from stromal cells revealed that IL-6 was produced constitutively, and its production was increased by treatment with TNF-α and IFN-γ. In contrast IL-1, IL-2, IL-4, IL-7, IL-8, IL-10, IL-12, TNF-α, and IFNγ were not produced. Functional tests showed that these cells express follicular dendritic cell-like properties. Coculturing of tonsilar B cells with stromal cells resulted in enhanced proliferation and also led to increased production of immunoglobulins and IL-6, suggesting crucial signaling between these populations

Identification of receptor-type protein tyrosine phosphatase μ as a new marker for osteocytes

Osteocytes are the predominant cells in bone, where they form a cellular network and display important functions in bone homeostasis, phosphate metabolism and mechanical transduction. Several proteins strongly expressed by osteocytes are involved in these processes, e.g., sclerostin, DMP-1, PHEX, FGF23 and MEPE, while others are upregulated during differentiation of osteoblasts into osteocytes, e.g., osteocalcin and E11. The receptor-type protein tyrosine phosphatase µ (RPTPμ) has been described to be expressed in cells which display a cellular network, e.g., endothelial and neuronal cells, and is implied in mechanotransduction. In a capillary outgrowth assay using metatarsals derived from RPTPμ-knock-out/LacZ knock-in mice, we observed that the capillary structures grown out of the metatarsals were stained blue, as expected. Surprisingly, cells within the metatarsal bone tissue were positive for LacZ activity as well, indicating that RPTPμ is also expressed by osteocytes. Subsequent histochemical analysis showed that within bone, RPTPμ is expressed exclusively in early-stage osteocytes. Analysis of bone marrow cell cultures revealed that osteocytes are present in the nodules and an enzymatic assay enabled the quantification of the amount of osteocytes. No apparent bone phenotype was observed when tibiae of RPTPμ-knock-out/LacZ knock-in mice were analyzed by μCT at several time points during aging, although a significant reduction in cortical bone was observed in RPTPμ-knock-out/LacZ knock-in mice at 20 weeks. Changes in trabecular bon

Serotonin and poor neonatal adaptation after antidepressant exposure in utero

Objective Infants exposed to selective antidepressants (SADs) in utero are at risk to develop poor neonatal adaptation (PNA) postpartum. As symptoms are non-specific and the aetiology of PNA is unknown, the diagnostic process is hampered. We hypothesised that the serotonin metabolism plays a role in the aetiology of PNA. Methods In this controlled study, infants admitted postpartum from February 2012 to August 2013 were included and followed for 3 days. Infants exposed to SADs during at least the last 2 weeks of fetal life were included in the patient group (n=63). Infants not exposed to psychotropic medication and admitted postpartum for another reason were included in the control group (n=126). The neonatal urinary 5-hydroxyindoleacetid acid (5-HIAA) levels of SAD-exposed infants who developed PNA, SAD-exposed infants who did not develop PNA and control infants were compared. Results The course of the 5-HIAA levels over the first 3 days postpartum differed between infants with and without PNA (p≤0.001) with higher 5-HIAA levels in infants with PNA on day 1 (2.42 mmol/mol, p=0.001). Presence of maternal psychological distress modified this relationship. Conclusions A transient disturbance of the neonatal serotonergic system may play a role in the aetiology of PNA. Other factors, including the presence of maternal psychological distress, also seem to play a role

Prevalence of heart failure and left ventricular dysfunction in the general population; The Rotterdam Study

AIMS: To determine the prevalence of heart failure and symptomatic as well as asymptomatic left ventricular systolic dysfunction in the general population. METHODS AND RESULTS: In 5540 participants of the Rotterdam Study (age 68.9+/-8.7 years, 2251 men) aged 55-95 years, the presence of heart failure was determined by assessment of symptoms and signs (shortness of breath. ankle oedema and pulmonary crepitations) and use of heart failure medication. In 2267 subjects (age 65.7+/-7.4 years, 1028 men) fractional shortening was measured. The overall prevalence of heart failure was 3.9% (95% CI 3.0+/-4.7) and did not differ between men and women. The prevalence increased with age, with the exception of the highest age group in men. Fractional shortening was higher in women and did not decrease appreciably with age. The prevalence of left ventricular systolic dysfunction (fractional shortening <=25%) was approximately 2.5 times higher in men (5.5%, 95% CI 4.1-7.0) than in women (2.2%, 95% CI 1.4-3.2). Sixty percent of persons with left ventricular systolic dysfunction had no symptoms or signs of heart failure at all. CONCLUSIONS: The prevalence of heart failure is appreciable and does not differ between men and women. The majority of persons with left ventricular systolic dysfunction can be regarded as having asymptomatic left ventricular systolic dysfunction