Risks of myeloid malignancies in patients with autoimmune conditions

Autoimmune conditions are associated with an elevated risk of lymphoproliferative malignancies, but few studies have investigated the risk of myeloid malignancies. From the US Surveillance Epidemiology and End Results (SEER)-Medicare database, 13 486 myeloid malignancy patients (aged 67+ years) and 160 086 population-based controls were selected. Logistic regression models adjusted for gender, age, race, calendar year and number of physician claims were used to estimate odds ratios (ORs) for myeloid malignancies in relation to autoimmune conditions. Multiple comparisons were controlled for using the Bonferroni correction (P<0.0005). Autoimmune conditions, overall, were associated with an increased risk of acute myeloid leukaemia (AML) (OR 1.29) and myelodysplastic syndrome (MDS, OR 1.50). Specifically, AML was associated with rheumatoid arthritis (OR 1.28), systemic lupus erythematosus (OR 1.92), polymyalgia rheumatica (OR 1.73), autoimmune haemolytic anaemia (OR 3.74), systemic vasculitis (OR 6.23), ulcerative colitis (OR 1.72) and pernicious anaemia (OR 1.57). Myelodysplastic syndrome was associated with rheumatoid arthritis (OR1.52) and pernicious anaemia (OR 2.38). Overall, autoimmune conditions were not associated with chronic myeloid leukaemia (OR 1.09) or chronic myeloproliferative disorders (OR 1.15). Medications used to treat autoimmune conditions, shared genetic predisposition and/or direct infiltration of bone marrow by autoimmune conditions, could explain these excess risks of myeloid malignancies

Increase of SERS Signal Upon Heating or Exposure to a High-Intensity Laser Field: Benzenethiol on an AgFON Substrate

The surface-enhanced Raman scattering (SERS) signal from an AgFON plasmonic substrate, recoated with benzenethiol, was observed to increase by about 100% upon heating for 3.5 min at 100C and 1.5 min at 125C. The signal intensity was found to increase further by about 80% upon a 10 sec exposure to a high-intensity (3.2 kW/cm^2) 785-nm cw laser, corresponding to 40 mW in a 40+/-5-um diameter spot. The observed increase in the SERS signal may be understood by considering the presence of benzenethiol molecules in an intermediate or 'precursor' state in addition to conventionally ordered molecules forming a self-assembled monolayer. The increase in the SERS signal arises from the conversion of the molecules in the precursor state to the chemisorbed state due to thermal and photo-thermal effects.Comment: 9 pages, 4 figures; J. Phys. Chem. C, accepte

Distinct Populations of Hepatic Stellate Cells in the Mouse Liver Have Different Capacities for Retinoid and Lipid Storage

Hepatic stellate cell (HSC) lipid droplets are specialized organelles for the storage of retinoid, accounting for 50–60% of all retinoid present in the body. When HSCs activate, retinyl ester levels progressively decrease and the lipid droplets are lost. The objective of this study was to determine if the HSC population in a healthy, uninjured liver demonstrates heterogeneity in its capacity for retinoid and lipid storage in lipid droplets. To this end, we utilized two methods of HSC isolation, which leverage distinct properties of these cells, including their vitamin A content and collagen expression. HSCs were isolated either from wild type (WT) mice in the C57BL/6 genetic background by flotation in a Nycodenz density gradient, followed by fluorescence activated cell sorting (FACS) based on vitamin A autofluorescence, or from collagen-green fluorescent protein (GFP) mice by FACS based on GFP expression from a GFP transgene driven by the collagen I promoter. We show that GFP-HSCs have: (i) increased expression of typical markers of HSC activation; (ii) decreased retinyl ester levels, accompanied by reduced expression of the enzyme needed for hepatic retinyl ester synthesis (LRAT); (iii) decreased triglyceride levels; (iv) increased expression of genes associated with lipid catabolism; and (v) an increase in expression of the retinoid-catabolizing cytochrome, CYP2S1. Conclusion: Our observations suggest that the HSC population in a healthy, uninjured liver is heterogeneous. One subset of the total HSC population, which expresses early markers of HSC activation, may be “primed” and ready for rapid response to acute liver injury