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A girl with acute lymphoblastic leukemia in remission had two seizures during the maintenance phase of her treatment. Magnetic resonance imaging with angiography identified a superior sagittal sinus thrombosis as the likely explanation for her symptoms. Possible causes are considered, and previous reports of the neurotoxicity of agents used in the treatment of leukemia are reviewed.

Partially deuterated (DPE) and conventional (PE) polyethylene are used to study chain conformations in melt-crystallized blends. The deuterium fraction γ ranged from 0.19 to 0.59, resulting in melting temperature differences ΔTm=1–2°C between PE and DPE. Small-angle neutron scattering (SANS) from molten or quench-crystallized blends yields single-chain radii of gyration Rg which apparently depend on γ and are as much as 15% larger than values reported from experiments with fully labelled (γ=1) polyethylene. Quenched PE/DPE blends give Gaussian-like scattering patterns out to q=O.l A −1 , the limit of these studies. This implies considerably more intramolecular correlations at distances of 10–50 A than derived from a similar experiment employing fully deuterated chains. The present result is thought to be more representative of semicrystalline polyethylene since DPE and PE are nearly perfectly matched. Crystallization by slow cooling creates non-statistical concentration fluctuations which result in excess forward SANS, so a melting point difference of 1°C is still sufficient to trigger `clustering' or ‘segregation’ of PE and DPE. Intensity decays at q > 0.05 A −1 to the same value as in quenched samples, regardless of crystallinity changing from 0.52 to 0.74. These results are shown to be consistent with dominant ‘near-adjacent re-entry’ during crystallization of polyethylene from the melt.

Aberrant Wnt signaling due to deregulation of Wnt regulators is implicated in the development and progression of numerous embryonal tumors. This study addresses the questions if activation of Wnt signaling in germ cell tumors (GCTs) arising during childhood and adolescence is associated with aberrations of the tumor suppressor adenomatous polyposis coli (APC), and whether APC aberrations might be responsible for progression from benign teratoma to malignant yolk sac tumor (YST).Forty-eight GCTs were analyzed, including mature (n = 5) and immature (n = 7) teratomas, mixed malignant GCTs (n = 10), YSTs (n = 17) as well as dysgerminomas (n = 9). To screen APC for genetic aberrations, we conducted direct sequencing of the mutation cluster region (MCR), loss of heterozygosity analyses (LOH) and protein truncation test. Epigenetic analyses included methylation specific PCR and bisulfite genomic sequencing of the APC 1a promoter. Gene expression was determined by quantitative real-time PCR.Aberrant promoter methylation was detected in YSTs, teratomas and mixed malignant GCTs, with a pronounced hypermethylation exclusively in YSTs (11/13) while dysgerminomas were not methylated (0/9). Teratomas (2/2) and YSTs (4/5) show LOH at the APC locus. However, neither mutations within the MCR nor truncated protein were detected. APC expression did not significantly vary between the different histological subgroups.Methylation of APC and LOH 5q21-22 in YSTs and teratomas provide evidence for involvement of APC in the accumulation of β-catenin and activation of the WNT pathway. Our additional analyses suggest that APC is unlikely to be solely responsible for the formation and progression of childhood GCTs.

Malignant germ cell tumors (GCT) of childhood are rare and heterogeneous neoplasms thought to arise from primordial germ cells. They vary substantially in their natural history and show important clinical differences from their adult counterparts. To address the biological basis for these observations, we have undertaken a comprehensive analysis of global gene expression patterns in pediatric malignant GCTs and compared these findings with published data on adult testicular GCTs (TGCT). Our study included 27 primary tumors and assessed the principal malignant histologic types of pediatric GCT, yolk sac tumor (YST; n = 18), and seminoma (n = 9). Analysis of Affymetrix U133A GeneChip data was performed using the statistical software environment R, including gene set enrichment analysis, with cross-validation at the RNA and protein level. Unsupervised analysis showed complete separation of YSTs and seminomas by global gene expression profiles and identified a robust set of 657 discriminatory transcripts. There was no segregation of tumors of the same histology arising at different sites or at different ages within the pediatric range. In contrast, there was segregation of pediatric malignant GCTs and adult malignant TGCTs, most notably for the YSTs. The pediatric seminomas were significantly enriched for genes associated with the self-renewing pluripotent phenotype, whereas the pediatric YSTs were significantly enriched for genes associated with a differentiation and proliferation phenotype. We conclude that histologic type is the key discriminator in pediatric malignant GCTs and that the observed clinical differences between malignant GCTs of children and adults are mirrored by significant differences in global gene expression. [Cancer Res 2008;68(11):4239–47]

Small-angle neutron scattering is used to evaluate the binary interaction parameter χ in molten blends of polyethylenes having different levels of ethyl branching along the backbone. The labelled chains were partially deuterated to minimize the isotope effect on χ. The present results for equal-volume-fraction binary blends at 150°C can be summarized as χ =0.4×10 −4 +0.014 ΔX 2 br . The first term is from the hydrogen-deuterium isotope effect for chains labelled with about 33% deuterium. The second term is due to chemical composition differences, expressed here as the difference in X br , the fraction of four-carbon repeat units having an ethyl branch. The observed contributions to χ are in reasonable accord with calculated estimates.

Several disorders of hypomagnesaemia of hetary renal origin are now recognised. The cases of two sisters from a consanguineous marriage with the syndrome of renal magnesium wasting, hypercalciuria and nephrocalcinosis are presented. Pathological examination of the heterozygous parental kidneys revealed mild focal interstitial fibrosis. This condition is a previously unreported cause of end-stage renal failure in chilhhood, and this report suggests that transplantation from heterozygous parental donors can be successfully undertaken without recurrence currence of the syndrome.