Human FDC express PrPc in vivo and in vitro

Prion diseases are fatal neurodegenerative disorders caused by accumulation of abnormal prion protein (protease-resistant prion, PrPres). PrPres accumulation is also detected in lymphoid organs after peripheral infection. Several studies suggest that follicular dendritic cells (FDC) could be the site of PrPres retention and amplification

Do Bovine Lymphocytes Express a Peculiar Prion Protein?

The cellular prion protein (PrPc) is a glycolipid-anchored cell surface protein that usually exhibits three glycosylation states. Its post-translationally modified isoform, PrPsc, is involved in the pathogenesis of various transmissible spongiform encephalopathies (TSEs). In bovine species, BSE infectivity appears to be restricted to the central nervous system; few or no detectable infectivity is found in lymphoid tissues in contrast to scrapie or variant CJD. Since expression of PrPc is a prerequisite for prion replication, we have investigated PrPc expression by bovine immune cells. Lymphocytes from blood and five different lymph organs were isolated from the same animal to assess intra- and interindividual variability of PrPc expression, considering six individuals. As shown by flow cytometry, this expression is absent or weak on granulocytes but is measurable on monocytes, B and T cells from blood and lymph organs. The activation of the bovine cells produces an upregulation of PrPc. The results of our in vitro study of PrPc biosynthesis are consistent with previous studies in other species. Interestingly, western blotting experiments showed only one form of the protein, the diglycosylated band. We propose that the glycosylation state could explain the lack of infectivity of the bovine immune cells

Infliximab then efalizumab, the 'hit and run' approach does not work

BACKGROUND: In a previous paper we described 2 patients treated with a sequential biologic therapy for chronic plaque psoriasis. We used infliximab as an induction treatment followed by efalizumab. We extended this approach to 3 other patients. OBJECTIVE: The purpose was to show the feasibility of a sequential approach with biologicals. METHODS: Five patients received three infusions of infliximab followed by weekly injections of efalizumab from week 10 on. RESULTS: The most important findings, summarized in a table, show that none of the patients continued the treatment for more than a year either because of non-responsiveness or because of spontaneous stopping. Moreover, 4 out of 5 patients did not respond or had serious adverse events on reintroduction of infliximab. CONCLUSION: Overall, we cannot recommend sequential therapy using infliximab and efalizumab

Expression of SV2 isoforms during rodent brain development

BACKGROUND: SV2A, SV2B and SV2C are synaptic vesicle proteins that are structurally related to members of the major facilitator superfamily (MFS). The function and transported substrate of the SV2 proteins is not clearly defined although they are linked to neurotransmitters release in a presynaptic calcium concentration-dependent manner. SV2A and SV2B exhibit broad expression in the central nervous system while SV2C appears to be more restricted in defined areas such as striatum. SV2A knockout mice start to display generalized seizures at a late developmental stage, around post-natal day 7 (P7), and die around P15. More recently, SV2A was demonstrated to be the molecular target of levetiracetam, an approved anti-epileptic drug (AED). The purpose of this work was to precisely analyze and quantify the SV2A, SV2B and SV2C expression during brain development to understand the contribution of these proteins in brain development and their impact on epileptic seizures. RESULTS: First, we systematically analyzed by immunohistofluorescence, the SV2A, SV2B and SV2C expression during mouse brain development, from embryonic day 12 (E12) to P30. This semi-quantitative approach suggests a modulation of SV2A and SV2B expression in hippocampus around P7. This is the reason why we used various quantitative approaches (laser microdissection of whole hippocampus followed by qRT-PCR and western blot analysis) indicating that SV2A and SV2B expression increased between P5 and P7 and remained stable between P7 and P10. Moreover, the increase of SV2A expression in the hippocampus at P7 was mainly observed in the CA1 region while SV2B expression in this region remains stable. CONCLUSIONS: The observed alterations of SV2A expression in hippocampus are consistent with the appearance of seizures in SV2A−/− animals at early postnatal age and the hypothesis that SV2A absence favors epileptic seizures around P7

Levels and profiles of PCDDs, PCDFs and cPCBs in Belgian breast milk. Estimation of infant intake

Congener-specific analyses of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and non-ortho (coplanar) polychlorinated biphenyls (cPCBs) were performed on 20 non-pooled breast milk samples collected in or close to an industrial area of Wallonia (Belgium). PCDD/F concentrations ranged between 16.0 and 52.1 pg TEQ/g fat, with a mean value of 29.4 pg TEQ/g fat. If coplanar PCBs (77, 126, 169) are included in TEQ calculations, levels ranged between 22.2 and 100.2 pg TEQ/g fat, with a mean value of 40.8 pg TEQ/g fat. It appears that 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, 2,3,4,7,8-PeCDF and PCB-126 account for more than 90% of the TEQ. Estimated PCDD/F dietary intake is 76 pg TEQ/kg body weight (bw)/day. This value is almost 20 times higher than the World Health Organization tolerable daily intake. A value of 103 pg TEQ/kg bw/day represents the intake of PCDDs, PCDFs and cPCBs (no mono-ortho PCBs included). (C) 2002 Published by Elsevier Science Ltd

Molecular classification of T-cell lymphomas.

T-cell neoplasms encompass a heterogeneous group of relatively rare disease entities. This review, focused on lymphoblastic tumors (T-ALL/LBL) and nodal-based peripheral T-cell lymphomas (PTCL), summarizes recent advances in the molecular characterization of these diseases. In T-ALL/LBL, molecular subgroups delineated by gene expression profiling correlate with leukemic arrest at specific stages of normal thymocyte development and different oncogenic pathways, and seem to be of interest for prognosis prediction. Angioimmunoblastic T-cell lymphoma (AITL), one of the most common PTCL entities, comprises neoplastic cells with a molecular signature similar to normal follicular helper T cells, and this cellular derivation might account for several of the peculiar aspects of this disease. Except in ALK-positive anaplastic large cell lymphoma, defined by ALK gene fusions, chromosomal translocations are otherwise rare in PTCLs, but some recurrent rearrangements might be associated with distinct lymphoma subtypes. In PTCL, not otherwise specified (PTCL, NOS), novel molecular biomarkers of potential therapeutic interest have been recently identified

The effect of a straw dispenser on behavior and lesions in weanling pigs

Slatted floors and liquid manure–handling systems in intensive housing systems preclude the use of large straw quantities as enrichment material for pigs. Consequently, there is a need for alternative enrichment strategies, for example, by using suitable applications providing pigs with small straw quantities, which are associated with low straw waste. The aim of this study was to evaluate the effects of a straw dispenser filled with fully chopped straw on the behavior and lesions in weanling pigs. A total of 365 weanling pigs, housed in single-sex groups (gilts and intact boars), were randomly divided in 2 groups. Half of the pigs had access to a straw dispenser (straw; n = 187), and the other half had no access to straw (control; n = 178). They were housed in the weanling unit for a period of 7 weeks (7-20 kg) and received liquid feed. One straw dispenser was provided per pen, accessible to 3 pigs at a time of 10 to 15 pigs in the pen, and positioned above the feed trough. To receive straw, pigs had to manipulate the dispensing unit on the bottom of the dispenser. Behavioral observations were carried out twice a week, and present lesions were also scored on these days by the same observer. Data were analyzed using a logistic mixed model and a Fisher exact test. No differences were found for biting behavior toward different body parts between control and straw pigs. There was also no effect of gender. In boars, aggressive behavior occurred more in straw groups compared to control groups, which might be related to competition. This finding is also reflected in more lesions on the middle part of the body in straw groups. A lack of difference in lesion scores for tail and ears between the 2 groups suggests that the dispenser provided insufficient distraction for weanling pigs compared to a barren environment. However, the position of the straw dispenser must be kept in mind, as this caused pigs to perform straw-directed behavior mainly in the feed trough. In this study, based on behavioral observations and lesion scores, it seems that the straw dispenser did not provide pigs with more advantages compared to pigs in a barren environment. Moreover, competition was observed in pens with boars, which might be related to the fact that only one dispenser was provided per pen. It should, however, be taken into account that the position of the dispenser might not have been the most suitable as it possibly caused mixing of feed and straw.publisher: Elsevier articletitle: The effect of a straw dispenser on behavior and lesions in weanling pigs journaltitle: Journal of Veterinary Behavior: Clinical Applications and Research articlelink: http://dx.doi.org/10.1016/j.jveb.2016.02.001 content_type: article copyright: © 2016 Elsevier Inc. All rights reserved.status: publishe