“
“Chronic lymphocytic leukemia (CLL) is uniquely characterized by the existence of subsets of cases with quasi-identical, ‘stereotyped’ B-cell receptors (BCRs). Herein we investigate this stereotypy in 2662 patients with CLL, the largest series yet, using purpose-built bioinformatics methods based on sequence pattern discovery. selleck Besides improving the identification of ‘stereotyped’ cases, we demonstrate that CLL actually consists of two

different categories, based on the BCR repertoire, with important biological and ontogenetic differences. The first (similar to 30% of cases) shows a very restricted repertoire and is characterized by BCR stereotypy (clustered cases), whereas the second includes cases with heterogeneous BCRs (nonclustered

cases). Eleven major CLL clusters were identified with antigen-binding sites defined by just a few critically positioned residues, regardless of the actual immunoglobulin (IG) variable gene used. This situation is closely reminiscent of the receptors expressed by cells participating in innate immune responses. On these grounds, we argue that whereas CLL cases with heterogeneous BCRs likely derive from the conventional B-cell pool, cases with stereotyped BCRs could derive from progenitor cells evolutionarily adapted to particular antigenic challenges, perhaps intermediate between a true innate immune click here system and the conventional adaptive B-cell immune system, functionally similar to what has been suggested previously for mouse B1 cells. Leukemia (2010) 24, 125-132; doi:10.1038/leu.2009.186; published online 17 September

2009″
“In the CNS, lipocalin-type prostaglandin D synthase (L-PGDS) is predominantly a non-neuronal enzyme responsible for the production of PGD(2), an endogenous sleep promoting substance. We have previously demonstrated that estradiol differentially regulates L-PGDS transcript levels in the rodent brain. In hypothalamic nuclei, estradiol increases L-PGDS transcript expression, whereas in the ventrolateral preoptic area L-PGDS gene expression is reduced after estradiol treatment. In the present study, we Phospholipase D1 have used an immortalized glioma cell line transfected with a L-PGDS reporter construct and estrogen receptor (ER) alpha and EB beta expression plasmids to further elucidate the mechanisms underlying estradiol regulation of L-PGDS gene expression. We found that physiologically relevant concentrations of estradiol evoked an inverted U response in cells expressing ER alpha. The most effective concentration of estradiol (10(-11) M) increased the promoter activity 3-fold over baseline. Expression of ER beta did not increase activity over control and when ER beta was co-expressed with ER alpha there was a significant attenuation of the promoter activity. While ER alpha significantly increased L-PGDS promoter activity, our previous in vivo studies demonstrate a greater magnitude of change in L-PGDS gene expression in the presences of estradiol.