DNA methylation profiling in human B cells reveals immune regulatory elements and epigenetic plasticity at Alu elements during B-cell activation.

Memory is a hallmark of adaptive immunity, wherein lymphocytes mount a superior response to a previously encountered antigen. It has been speculated that epigenetic alterations in memory lymphocytes contribute to their functional distinction from their naive counterparts. However, the nature and extent of epigenetic alterations in memory compartments remain poorly characterized.

DNA methylation prevents CTCF-mediated silencing of the oncogene BCL6 in B cell lymphomas.

Aberrant DNA methylation commonly occurs in cancer cells where it has been implicated in the epigenetic silencing of tumor suppressor genes. Additional roles for DNA methylation, such as transcriptional activation, have been predicted but have yet to be clearly demonstrated. The BCL6 oncogene is implicated in the pathogenesis of germinal center-derived B cell lymphomas.

Selective targeting of nanocarriers to neutrophils and monocytes.

We previously identified and characterized cell-type selective binding peptides from random peptide phage display libraries. Here, we used one of these peptides (GGP) to target liposomal nanocarriers to leukocyte subsets. To profile the binding selectivity of GGP-coated liposomes to human blood cells, we performed flow cytometric analysis with whole anti-coagulated blood.

The BCL6-associated transcriptional co-repressor, MTA3, is selectively expressed by germinal centre B cells and lymphomas of putative germinal centre derivation.

Metastasis-associated protein 3 (MTA3) is a recently described cell-type specific component of the Mi-2-NURD transcriptional co-repressor complex that is expressed in breast epithelia and germinal centre B cells. In model B cell lines, MTA3 physically interacts with BCL6 and appears to be instrumental in maintenance of the germinal centre B cell transcriptional programme that precludes premature plasmacytic differentiation. Here, we report selective, in situ cell-type specific expression of MTA3 among lymphoid cells largely confined to the germinal centre B cell compartment.

Expression of the plasmacytoid dendritic cell marker BDCA-2 supports a spectrum of maturation among CD4+ CD56+ hematodermic neoplasms.

CD4+CD56+ hematodermic neoplasms are rare, aggressive hematopoietic malignancies usually presenting with cutaneous masses followed by a leukemic phase. The blastic morphology, CD56 expression and lack of definitive myeloid or T-cell markers initially resulted in assignment of this tumor to the NK-cell lineage. Accumulating evidence now suggests that these neoplasms represent malignant counterparts to the plasmacytoid dendritic cell.

Direct fluorochrome labeling of phage display library clones for studying binding specificities: applications in flow cytometry and fluorescence microscopy.

Phage display technology is increasingly employed to identify high-affinity peptides and single-chain antibodies with binding specificities for a diversity of target types. The analysis of phage-binding sensitivity and specificity typically employs directly labeled secondary antiphage antibodies and potentially tertiary labels, such as fluorochromes and enzymes, when biotinylated antibodies are used. However, secondary or tertiary reagents may not be feasible or desirable for some target types and applications.

MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation.

The transcriptional repressor BCL-6 regulates B lymphocyte cell fate during the germinal center reaction by preventing terminal differentiation of B lymphocytes into plasma cells until appropriate signals are received. Here, we report a cofactor, MTA3, a cell type-specific subunit of the corepressor complex Mi-2/NuRD, for BCL-6-dependent cell fate determination. MTA3 is expressed in the same pattern in germinal centers as BCL-6.

Immune status of physically active women during lactation.

Purpose: The purpose of this study was to provide baseline data on immune status of exercising and sedentary exclusively lactating women. Dietary intake and body composition were also investigated to determine whether they related to immune function.

Methods: Healthy, exclusively breastfeeding women with a body mass index between 20 and 30 kg x m were studied at 3 months postpartum.

Use of real-time polymerase chain reaction to identify cell- and tissue-type-selective peptides by phage display.

Phage display approaches are used increasingly in efforts to identify cancer-specific binding peptides and antibodies. Phage-derived reagents are likely to have broad applications in diagnostic and research pathology. A critical element in the identification of cell or tissue-type-specific phage is the ability to reproducibly quantify bound or eluted phage at various stages of panning and screening procedures.

MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer.

Estrogen receptor is a key regulator of proliferation and differentiation in mammary epithelia and represents a crucial prognostic indicator and therapeutic target in breast cancer. Mechanistically, estrogen receptor induces changes in gene expression through direct gene activation and also through the biological functions of target loci. Here, we identify the product of human MTA3 as an estrogen-dependent component of the Mi-2/NuRD transcriptional corepressor in breast epithelial cells and demonstrate that MTA3 constitutes a key component of an estrogen-dependent pathway regulating growth and differentiation.

Effect of exercise on immunologic factors in breast milk.

Objective: Although it is well documented that breast milk provides optimal nutrition and immune benefits to the infant, factors that influence the immunologic composition of breast milk are less understood. A recent study reported that immunoglobulin A (IgA) levels in breast milk are lower after exercise compared with resting concentrations. However, the women exercised until exhaustion.

Enrichment of LDL with EPA and DHA decreased oxidized LDL-induced apoptosis in U937 cells.

Oxidized LDL (oxLDL) may contribute to the accumulation of apoptotic cells in atherosclerotic plaques. Although it is well established in monophasic chemical systems that the highly unsaturated EPA and DHA will oxidize more readily than FA that contain fewer double bonds, our previous studies showed that enrichment of LDL, which has discrete polar and nonpolar phases, with these FA did not increase oxidation. The objective of this study was to compare the extent of apoptosis induced by EPA/DHA-rich oxLDL to that induced by EPA/DHA-non-rich oxLDL in U937 cells.

Trans-10, cis-12, but not cis-9, trans-11, conjugated linoleic acid attenuates lipogenesis in primary cultures of stromal vascular cells from human adipose tissue.

We have previously shown that both a commercially available mixture of conjugated linoleic acid (CLA) isomers and the trans-10, cis-12 isomer of CLA reduced the triglyceride (TG) content and induced apoptosis in differentiating cultures of murine 3T3-L1 preadipocytes. However, the influence of CLA isomers on differentiating human (pre)adipocytes is unknown. Therefore, we conducted a series of studies using primary cultures of stromal vascular cells isolated from human adipose tissue to determine: 1) the influence of seeding density and thiazolidinedione (TZD) concentration on TG content; 2) the chronic dose response of cis-9, trans-11 CLA vs.

Epigallocatechin gallate protects U937 cells against nitric oxide-induced cell cycle arrest and apoptosis.

Ingesting phenolic phytochemicals in many plant products may promote health, but the effects of phenolic phytochemicals at the cellular level have not been fully examined. Thus, it was determined if the tea phenolic phytochemical, epigallocatechin gallate (EGCG), protects U937 human pro-monocytic cells against the nitrogen free radical, nitric oxide (*NO). Cells were incubated for 4-6 h with 500 microM S-nitrosoglutathione (GSNO), which generates *NO, but this did not induce single-strand breaks in DNA.

Conjugated linoleic acid suppresses triglyceride accumulation and induces apoptosis in 3T3-L1 preadipocytes.

Four sets of experiments were conducted to examine the influence of conjugated linoleic acid (CLA) isomers during proliferation and differentiation of cultures of 3T3-L1 preadipocytes using physiological culturing conditions. Cultures treated with either albumin [bovine serum albumin (BSA) vehicle] or linoleic acid (LA) served as controls. For the proliferation study (Expt.

Dehydroepiandrosterone alters the growth of stromal vascular cells from human adipose tissue.

Objective: The purpose of this study was to determine if the antiobesity actions of dehydroepiandrosterone (DHEA) observed in vivo are due to an influence on the proliferation and differentiation of primary cultures of stromal-vascular (SV) cells isolated from human adipose tissue.

Design: SV cells were isolated from subcutaneous adipose tissue obtained from a young adult female undergoing elective liposuction. For the proliferation assay (Experiment 1), cultures were fed proliferation media containing 0, 5, 25 or 100 microM DHEA for 3d.