No abstract

Multiply branched polylactosaminoglycans are expressed in glycoproteins and glycolipids of many cells. Interest in their biology stems from their abundant expression in early embryonal cells and from their ability to carry multiple lectin-binding determinants, which makes them prominent ligands and antagonists of cell adhesion proteins. A prototype of their backbones is represented by the decasaccharide LacNAc beta1-3'(LacNAc beta1-6')LacNAc beta1-3'(LacNAc beta1-6')LacNAc (5), where LacNAc is the disaccharide Gal beta1-4GlcNAc. Here, we describe in vitro biosynthesis of glycan 5. Incubation of the linear hexasaccharide LacNAc beta1-3'LacNAc beta1-3'LacNAc (1) with UDP-GlcNAc and alpha midchain beta1,6-GlcNAc transferase activity (GlcNAc to Gal), present in rat serum [Gu, J., Nishikawa, A., Fujii, S., Gasa, S., & Taniguchi, N. (1992) J. Biol. Chem. 267, 2994-2999], gave the doubly branched octasaccharide LacNAc beta1-3'(GlcNAc beta1-6')LacNAc beta1-3'(GlcNAc beta1-6')LacNAc (4). The latter was converted to 5 by enzymatic beta1,4-galactosylation. In the initial branching reaction of 1, two isomeric heptasaccharide intermediates, LacNAc beta1-3'LacNAc beta1-3'(GlcNAc beta1-6')LacNAc (2) and LacNAc beta1-3'(GlcNAc beta1-6')LacNAc beta1-3'LacNAc (3), were formed first at comparable rates. Later, both intermediates were converted to 4, revealing two distinct pathways of the reaction: 1 --> 2 --> 4 and 1 --> 3 --> 4. These data suggest that, regardless of their chain length, linear polylactosamines similar to 1 contain potential branching sites at each of the internal galactoses. The enzyme-binding epitope of 1 is probably LacNAc beta1-3'LacNAc, because the trisaccharides GlcNAc beta1-3'LacNAc and LacNAc beta1-3Gal as well as the tetrasaccharide GlcNAc beta1-3'LacNAc beta1-3Gal were poor acceptors, while LacNAc beta1-3'LacNAc was a good one. Midchain beta1,6-GlcNAc transferase activities present in serum of several mammalian species, including man, resembled closely the rat serum activity in their mode of action and in their acceptor specificity. We suggest that analogous membrane-bound Golgi enzymes are involved in the biosynthesis of multiply branched polylactosamines in vivo.

With the increasing incidence of multiple sclerosis (MS) in women and the earlier use of disease modifying therapy (DMT), issues surrounding DMT and pregnancy are a regular subject of discussion with regards to optimal management. Current recommendations are to withdraw DMT prior to conception, leaving patients exposed to an uncertain period of untreated disease. The objective of this study is to report preliminary experience on glatiramer acetate (GA) exposure through conception, pregnancy and the post-partum period in a series of 13 patients with previously highly active relapsing-remitting MS. This is a prospective observational case series. Fourteen pregnancies of 13 women resulted in 13 live births (one twin pregnancy), nine exposed to GA throughout pregnancy. There were no birth defects and treatment was well tolerated. No relapses occurred during pregnancy in those continuing on treatment. In conclusion, our early experience suggests that when considering the risks and benefits of treatment withdrawal prior to pregnancy, it may be reasonable to continue GA in those patients with previously highly active disease. Consideration should also be given to the initiation of a birth register, similar to such initiatives in epilepsy, to generate more robust safety data in this controversial area.

LAG requires fewer anaesthetics, is associated with shorter time to feeding, shortened hospital stay and has a reduced risk of major complications. LAG is a very good alternative to the PEG in children.

Anaplastic ganglioglioma (AGG) are rare central nervous system tumours. Patient and treatment factors associated with outcome are poorly defined and limited to small retrospective case series and single case reports. Using the Surveillance, Epidemiology, and End Results (SEER) cancer registry, we investigated potential clinicopathological factors that can affect outcome in patients with anaplastic ganglioglioma. Patients with anaplastic ganglioglioma diagnosed between 1973 and 2007 were identified from the SEER database. Kaplan-Meier survival analysis and Cox models were used to examine the effect of variables on overall survival. The variables analysed included patient age at diagnosis, gender, race, tumour location, uni-focal or multi-focal tumour, surgical resection and the use of adjuvant radiotherapy. Fifty-eight patients were identified, with a median age at diagnosis of 25.5 years. Ninety-three percent of patients underwent surgery and 36% received adjuvant radiotherapy. The median overall survival was 28.5 months. The most common tumour site was the temporal lobe (27%). Univariate and multivariate analysis identified surgery and uni-focal disease as important predictors of overall survival. Adjuvant radiotherapy did not influence overall survival. This study represents the largest analysis of anaplastic ganglioglioma to date. Furthermore it also emphasises the role of national tumour databases for furthering our understanding of rare brain tumours and determining management options.