Tyrosine phosphorylation of annexin II tetramer is stimulated by membrane binding

In the present article we have examined if the interaction of the Ca2+-binding protein, annexin II tetramer (AIIt) with the plasma membrane phospholipids or with the submembranous cytoskeleton, effects the accessibility of the tyrosine phosphorylation site of AIIt. In the presence of Ca2+, pp60(c-src) catalyzed the incorporation of 0.22 +/- 0.05 mol of phosphate/mol of AIIt (mean +/- S.D., n = 5). The Ca2+-dependent binding of AIIt to purified adrenal medulla plasma membrane or phosphatidylserine vesicles stimulated the pp60(c-src)-dependent phosphorylation of AIIt to 0.62 +/- 0.04 mol of phosphate/mol of AIIt (mean +/- S.D., n = 5) or 0.93 +/- 0.07 mol of phosphate/mol of AIIt (mean +/- S.D., n = 5), respectively. Phosphatidylserine- or phosphatidylinositol-containing vesicles but not vesicles composed of phosphatidylcholine or phosphatidylethanolamine, stimulated the phosphorylation of AIIt. In contrast, the binding of AIIt to F-actin resulted in the incorporation of only 0.04 +/- 0.04 mol of phosphate/mol of AIIt (mean +/- S.D., n = 5). These results suggest that the interaction of AIIt with plasma membrane and not the submembranous cytoskeleton, activates the tyrosine phosphorylation of AIIt by inducing a conformational change in the protein resulting in the enhanced exposure or accessibility of the tyrosine-phosphorylation site.     

Correlation of chromosome 17p loss with clinical outcome in medulloblastoma

Medulloblastomas are primitive neuroectodermal tumors that arise in the cerebella of children. Cytogenetic and loss of heterozygosity (LOH) studies have shown that deletions on the short arm of chromosome 17 occur in 25-50% of cases, suggesting that loss of a tumor suppressor gene located on 17p plays a role in the genesis or progression of medulloblastoma. We report here on an LOH analysis of 21 patients with medulloblastoma using markers for 15 polymorphic loci previously ordered on chromosome 17 by meiotic break point mapping. Although the frequency of LOH in our patients (48%) was consistent with previous reports, our maps showed much larger deletions, the smallest spanning a 38-cM genetic distance distal to marker UT49 (D17S731). Survival analysis did not show a significant association between LOH on 17p and survival, although the sample size was too small to rule out a difference of less than 10-fold. Clinical risk factors were better prognostic indicators than LOH, with significantly prolonged survival in patients free of craniospinal metastasis following gross total tumor resection.     

Logistics and design issues in the use of biological samples in observational epidemiology

Standard epidemiological study designs are well suited to answering questions involving the collection of biological samples. However, different designs are better suited--both for design and logistic reasons--to different questions. The strengths and weaknesses of each design are discussed in relation to markers of exposure, susceptibility and early outcome, and to markers used to classify cancers into biologically defined subsets.