1,720,970 research outputs found
High CCR5 expression in natalizumab-associated progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome supports treatment with the CCR5 inhibitor maraviroc
No full textHigh CCR5 expression in natalizumab-associated progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome supports anti CCR5 therapy
No full textImpaired remyelination in late-onset multiple sclerosis
No full textAbstract A reduced regenerative capacity may contribute to faster disease progression and poorer relapse recovery in multiple sclerosis patients with disease onset after the age of 50, a condition known as late-onset multiple sclerosis (LOMS). We hypothesized that lesions in LOMS patients show more pronounced axonal damage, less remyelination and an altered inflammatory composition, and performed a detailed histopathological analysis of MS biopsies in patients with early-stage LOMS. The number of T cells, B cells, plasma cells, microglia/macrophages, different oligodendrocyte populations as well as the axonal density and acute axonal damage were assessed in 31 LOMS and 30 normal-onset MS (NOMS, 20–40 years old) patients. No major differences in the inflammatory infiltrate or axonal damage were found. BCAS1-positive oligodendrocytes indicating early myelinating oligodendrocytes, and mature oligodendrocytes were significantly lower in the normal-appearing white matter of LOMS compared to NOMS patients ( p = 0.05; p = 0.01), with a negative correlation with age (r = − 0.5, p = 0.01). In active demyelinating lesions, the number of BCAS1-positive oligodendrocytes did not differ between LOMS and NOMS, but NOMS lesions showed a higher proportion of ramified cells indicating active remyelination. In LOMS, BCAS1-positive oligodendrocytes decreased with increasing lesion age, with the lowest numbers found in inactive demyelinated lesions. In contrast, NOMS patients showed high numbers of BCAS1-positive cells with an activated morphology, even in inactive demyelinated lesions. At the last follow-up, LOMS patients had a significantly higher EDSS score (median 3.5) than NOMS patients (median 3.0, p = 0.05). A higher EDSS score correlated with fewer mature and oligodendrocyte precursor cells in active demyelinating lesions (r = − 0.4, p = 0.01 and r = − 0.6, p = 0.003). These findings suggest a clinically relevant impaired oligodendrocyte differentiation and remyelination in LOMS. Since remyelination is essential for axonal protection, it will be necessary to consider the complex and dynamic tissue environment when researching therapeutics aimed at fostering the differentiation of oligodendrocyte precursor cells into myelinating oligodendrocytes.Sanofi-Aventis Deutschland https://doi.org/10.13039/100019944Herzzentrum Göttinge
Apheresis therapy in multiple sclerosis patients with histopathologically classified immunopathological patterns
No full textTeva Pharma; Biogen; Novartis; Genzym
Neurofilament light chains in serum as biomarkers of axonal damage in early MS lesions: a histological–serological correlative study
No full textAbstract
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease associated with axonal injury, and neurofilament light chains in serum (sNfL) are considered a biomarker for this damage. We aimed to investigate the relationship between sNfL and the axonal damage in early MS lesions in a special cohort of biopsied patients. sNfL from 106 biopsied patients with 26 follow-up samples were analyzed using single-molecule array (SiMoA) technology. Findings were correlated with clinical parameters and histological findings of acute axonal damage (APP-positive spheroids) and axonal loss in different lesion stages. A median of 59 pg/ml sNfL was found (range 8–3101 pg/ml). sNfL levels correlated with APP-positive spheroids in early active demyelinating lesions that represent the earliest lesion stages (
p
< 0.01). A significant negative correlation between sNfL levels in follow-up blood samples and axonal density in normal-appearing white matter was also observed (
p
= 0.02). sNfL levels correlated with the Expanded Disability Status Score at biopsy (
p
< 0.01,
r
= 0.49) and at last clinical follow-up (
p
< 0.01,
r
= 0.66). In conclusion, sNfL likely represent a compound measure of recent and ongoing neuroaxonal damage. We found that sNfL in biopsied MS patients correlate with acute axonal damage in the earliest MS lesion stages. Determination of sNfL levels thus allows insight into brain pathology and underlines the relevance of relapse-associated lesional pathology. Axonal loss in normal-appearing white matter contributes to sNfL levels independent of relapses. Since sNfL levels correlate with clinical disability, they may predict the future disability of patients and help with individual treatment decisions.Novartis Pharma http://dx.doi.org/10.13039/100008792Georg-August-Universität Göttingen 50110000338
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
CNS inflammation after natalizumab therapy for multiple sclerosis: A retrospective histopathological and CSF cohort study
No full textOpen-Access-Finanzierung durch die Universitätsmedizin Göttingen 202
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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