Tau in the brain interstitial fluid is fragmented and seeding-competent.

In Alzheimer disease, Tau pathology is thought to propagate from cell to cell throughout interconnected brain areas. However, the forms of Tau released into the brain interstitial fluid (ISF) in vivo during the development of Tauopathy and their pathological relevance remain unclear. Combining in vivo microdialysis and biochemical analysis, we find that in Tau transgenic mice, human Tau (hTau) present in brain ISF is truncated and comprises at least 10 distinct fragments spanning the entire Tau protein.

Collecting antibodies and large molecule biomarkers in mouse interstitial brain fluid: a comparison of microdialysis and cerebral open flow microperfusion.

The determination of concentrations of large therapeutic molecules, like monoclonal antibodies (mAbs), in the interstitial brain fluid (ISF) is one of the cornerstones for the translation from preclinical species to humans of treatments for neurodegenerative diseases. Microdialysis (MD) and cerebral open flow microperfusion (cOFM) are the only currently available methods for extracting ISF, and their use and characterization for the collection of large molecules in rodents have barely started. For the first time, we compared both methods at a technical and performance level for measuring ISF concentrations of a non-target-binding mAb, trastuzumab, in awake and freely moving mice.

Alternative splicing of the TNFSF13B (BAFF) pre-mRNA and expression of the BAFFX1 isoform in human immune cells.

Human B cell activating factor (TNFSF13B, BAFF) is a tumor necrosis factor superfamily member. Binding its unique receptor (TNFRSF13C, BAFF-R) mediates gene expression and cell survival in B cells via activation of NFκB pathway. Furthermore, there is data indicating a role in T cell function.

N368-Tau fragments generated by legumain are detected only in trace amount in the insoluble Tau aggregates isolated from AD brain.

Intraneuronal insoluble inclusions made of Tau protein are neuropathological hallmarks of Alzheimer Disease (AD). Cleavage of Tau by legumain (LGMN) has been proposed to be crucial for aggregation of Tau into fibrils. However, it remains unclear if LGMN-cleaved Tau fragments accumulate in AD Tau inclusions.

Levetiracetam but not valproate inhibits function of CD8+ T lymphocytes.

Purpose: To further elucidate possible immune-modulatory effects of valproate (VPA) or levetiracetam (LEV), we investigated their influence on apoptosis and cytotoxic function of CD8+ T lymphocytes in humans.

Methods: In 15 healthy subjects (9 female (60%), 35.7±12.

Sibling disability risk at onset and during disease progression in familial multiple sclerosis.

Background: The objective of this study was to address the differences in onset and disease progression between familial and sporadic multiple sclerosis (MS) and the association within sibling pairs.

Methods: Ninety-eight siblings and their controls were included from a database of 763 sporadic MS-patients, randomly pair-matched for age, gender, clinical course, disease duration and treatment. Sixty-eight available siblings completed a prospective six-year follow-up.

Clonal expansions of CD4+ B helper T cells in autoimmune myasthenia gravis.

The weakness in myasthenia gravis (MG) is mediated by T helper cell (Th)-dependent autoantibodies against neuromuscular epitopes. So far, analyzing Th phenotypes or antigen specificities has yielded very few clues to pathogenesis. Here we adopt an alternative antigen-independent approach, analyzing T cell receptor (TCR) Vbeta usage/expansions in blood from 118 MG patients.

Suppression of autoimmune encephalomyelitis by a neurokinin-1 receptor antagonist--a putative role for substance P in CNS inflammation.

Substance P (SP) is an excitatory neurotransmitter in the central and peripheral nervous system. Most of its physiological functions are mediated through binding to the neurokinin-1 receptor (NK-1R). Recently, proinflammatory properties of SP have been described.

Development and prevalidation of a list of structure-activity relationship rules to be used in expert systems for prediction of the skin-sensitising properties of chemicals.

The new European Union (EU) chemicals policy, as described in the White Paper entitled Strategy for a Future Chemicals Policy, has identified a need for computer-based tools suitable for predicting the hazardous properties of chemicals. Two sets of structural alerts (fragments of chemical structure) for the prediction of skin sensitisation hazard classification ("R43, may cause sensitisation by skin contact") have been drawn up, based on sensitising chemicals from a regulatory database (containing data for the EU notification of new chemicals). These alerts comprise 15 rules for chemical structures deemed to be sensitising by direct action of the chemicals with cells or proteins within the skin, and three rules for substructures that act indirectly, i.

Behaviour of beta 2-adrenoceptors on lymphocytes under continuous and pulsatile tocolysis with Fenoterol.

The present study investigates the population of beta 2-receptors on lymphocytes in pregnant women with premature labor between the 29th and 34th week of pregnancy. The population of receptors on lymphocytes correlates with that on the myometrium, which is not accessible for study during pregnancy. Fourteen patients received a pulsatile tocolysis, while ten women received a continuous tocolysis with Fenoterol.

Comparison of protein with DNA therapy for chronic myocardial ischemia using fibroblast growth factor-2.

Objective: Treatment of coronary disease by growth factors has become an increasingly used strategy for otherwise untreatable patients and is subject to a number of clinical studies. The aim is to stimulate the development of a sufficient collateral circulation and hereby to rescue cardiac function. The objective of our study was to compare the effectiveness of fibroblast growth factor-2 (FGF-2) as protein and as naked plasmid DNA in a porcine model of chronic myocardial ischemia.