Assessment for 11q and other chromosomal aberrations in large B-cell/high-grade B cell lymphomas of germinal center phenotype lacking BCL2 expression.

The WHO classifications of hematolymphoid malignancies have recognized several distinct entities within the large B cell lymphomas, including the more recently described high-grade B cell lymphoma with 11q aberration (HGBCL-11q). We utilized genomic array to assess for chromosome 11q abnormalities in a broad set of aggressive B cell lymphomas from 27 patients with a focus on younger adults. The findings suggest more frequent alterations of 11q in diffuse large B cell lymphoma (DLBCL)/HGBCL-GC BCL2-, in comparison to cases of Burkitt lymphoma (BL) or DLBCL-GC BCL2+, and confirm a low genomic complexity score of BL. Variability identified in patterns of 11q alterations suggests genomic array studies may afford value over FISH testing as we continue to understand HGBCL-11q as a distinct entity, and interrogate cases of DLBCL/HGBCL-GC BCL2-.

Modulation of the development of human monocyte-derived dendritic cells by lithium chloride.

Lithium has been used or explored to treat psychiatric and neurodegenerative diseases that are frequently associated with an abnormal immune status. It is likely that lithium may work through modulation of immune responses in these patients. Because dendritic cells (DC) play a central role in regulating immune responses, this study investigated the influence of lithium chloride (LiCl) on the development and function of DC. Exposure to LiCl during the differentiation of human monocyte-derived immature DCs (iDC) enhances CD86 and CD83 expression and increases the production of IL-1ß, IL-6, IL-8, IL-10, and TNF-α. However, the presence of LiCl during LPS-induced maturation of iDC has the opposite effect. During iDC differentiation, LiCl suppresses the activity of glycogen synthase kinase (GSK)-3ß, and activates PI3K and MEK. In addition, LiCl activates peroxisome proliferator-activated receptor γ (PPARγ) during iDC differentiation, a pathway not described before. Each of these signaling pathways appears to have distinct impact on the differentiating iDC. The enhanced CD86 expression by LiCl involves the PI3K/AKT and GSK-3ß pathway. LiCl modulates the expression of CD83 in iDC mainly through MEK/ERK, PI3K/AKT, and PPARγ pathways, while the increased production of IL-1ß and TNF-α mainly involves the MEK/ERK pathway. The effect of LiCl on IL-6/IL-8/IL-10 secretion in iDC is mediated through inhibition of GSK-3ß. We have also demonstrated that PPARγ is downstream of GSK-3ß and is responsible for the LiCl-mediated modulation of CD86/83 and CD1 expression, but not IL-6/8/10 secretion. The combined influence of these molecular signaling pathways may account for certain clinical effect of lithium.

Differential patterns of serum brain-derived neurotrophic factor levels in alcoholic patients with and without delirium tremens during acute withdrawal.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is associated with alcohol addiction and withdrawal-related neurotoxicity. Delirium tremens (DT) is the most serious complication of alcohol withdrawal syndrome (AWS). In this study, we explored the differences in serum BDNF levels, measured at baseline and 1 week after alcohol withdrawal among alcoholic patients with and without DT. METHODS: Sixty-five inpatients, fulfilling the DSM-IV criteria of alcohol dependence and admitted for alcohol detoxification, as well as 39 healthy control subjects were enrolled. The alcoholic patients were divided by the appearance of DTs into the DT group (n = 25) and non-DT group (n = 40). We collected blood samples of the patient groups on the first and seventh days of alcohol withdrawal and measured serum BDNF levels by sandwich enzyme-linked immunosorbent assay. RESULTS: Serum BDNF levels differed significantly among the three groups: (i) control group 14.8 ± 4.7 ng/ml; (ii) non-DT group 12.3 ± 3.3 ng/ml; (iii) DT group 6.2 ± 2.6 ng/ml (p < 0.001). One week after alcohol withdrawal, the BDNF levels increased significantly for both alcoholic groups. While non-DT group had comparable BDNF levels (13.4 ± 3.5 ng/ml) with controls, the DT group still exhibited lower levels (8.9 ± 4.4 ng/ml). CONCLUSIONS: This study suggests chronic drinking leads to a reduction in BDNF levels, and patients with more deficient BDNF expression are vulnerable to the development of DTs. Additionally, BDNF levels elevated after prompt alcohol detoxification treatment. These findings indicate that BDNF could involve modifying the phenotypes of AWS as well as the pertinent neuroadaptive processes of alcohol dependence.