Additional file 1: Table S1. of Long-term efficacy and safety of fingolimod in Japanese patients with relapsing multiple sclerosis: 3-year results of the phase 2 extension study

Duration of exposure to fingolimod in patients entering the extension study. Table S2. Plasma levels of liver enzymes at core study baseline and in the extension study. Table S3. Proportion of patients with normal and elevated levels of liver enzymes. Table S4. Proportion of patients with normal and decreased levels of hematological parameters. (DOCX 35 kb

Brain regions in which regional cerebral glucose metabolism was negatively correlated with psychophysical task response time.

<p>Brain regions in which regional cerebral glucose metabolism was negatively correlated with psychophysical task response time.</p

Results of the whole-brain voxel-based analyses.

<p>First row: The brain regions that exhibited regional cerebral glucose metabolic reductions in the 60 PD patients relative to 14 normal volunteers (p<0.05 uncorrected, extent threshold of 100 voxels). Second row and below: The brain regions in which the resting CMRglc was correlated with the RTs in the various psychophysical tasks (Global: second row, Local: third row, Mixed: fourth row) and the shift cost (fifth row) (<i>p</i><0.001 uncorrected, extent threshold of 100 voxels). PD, Parkinson’s disease; R, right; L, left.</p

Schematic illustrations of the psychophysical tasks.

<p>In both the Global and Local tasks, compound letter stimuli appeared after a 2-second presentation of a visual cue that indicated whether the target was a global or local letter. The subjects were instructed to respond orally to the target component of each compound letter stimulus as quickly as possible. In these tasks, the subjects maintained their attention on a single component of the compound letters (either the local or global component of the stimuli), and they were not required to reorient their attention. However, in the Mixed task, the cue that indicated the target component of the compound letter changed from trial to trial in a pseudorandom manner. The task required that the subjects switch their attention on the basis of the cue that was presented to them on each trial.</p

The results of the ROI-based stepwise multiple regression analyses.

<p>7 ROIs are shown in different colors: right DLPFC  =  red, left DLPFC  =  cyan, left VLPFC  =  yellow, right TPO  =  purple, left TPO  =  green, medial parietal cortex  =  white, and left posterior IT  =  blue. The scatterplots illustrate the relationship between the psychophysical task performance scores and the FDG-uptake values in the ROIs. DLPFC, dorsolateral prefrontal cortex; VLPFC, ventrolateral prefrontal cortex; TPO, temporo-parieto-occipital junction; posterior IT, posterior inferior temporal cortex; FDG, ¹⁸F-fluorodeoxyglucose.</p

Mean RTs and error rates in the psychophysical tasks.

<p>Comparisons that were significantly different are indicated with a * (p<0.05/3). There was a significant simple interaction between group and the Global/Mixed task factor (F = 5.99, p = 0.016), and there was a trend toward an interaction between the group and the Local/Mixed task factor (F = 5.63, p = 0.020). PD, Parkinson’s disease.</p

Demographic and clinical characteristics of patients with PD and control participants.

<p>PD, Parkinson’s disease; MMSE, Mini Mental State Examination; CDR, Clinical Dementia Rating; NPI, Neuropsychiatric Inventory; UPDRS-III, Unified Parkinson’s Disease Rating Scale-motor score; L, left; R, right; B, bilateral.</p

Additional file 4: of Human central nervous system astrocytes support survival and activation of B cells: implications for MS pathogenesis

Figure S3. IFNγ production by proliferative T-cells. Human B cells were cultured in transwell as described previously, either alone or with stimulated or unstimulated astrocytes. Following 2 days in culture, B cells were harvested, thoroughly washed and co-cultured with human T cells from allogeneic donors at a B-cell:T-cell ratio of 1:4. Conditioned media of B-cell:T-cell co-culure was collected and IFNγ was measured using ELISA (representative experiment). (TIFF 7670 kb

Additional file 2: of Human central nervous system astrocytes support survival and activation of B cells: implications for MS pathogenesis

Figure S1. Confirming activation of human astrocytes. Astrocytes were cultured for 24 h and were either left unstimulated or were stimulated with IFNγ (10 ng/ml) and IL-1β (10 ng/ml). After 24 h, the astrocytes were washed thoroughly and fresh medium was added. After an additional 24 h in culture, at which time cultures were imaged and supernatants were collected for subsequent measurement of astrocyte-secreted IL-6 by ELISA. Compared to unstimulated astrocytes (a), stimulated astrocytes exhibited activated morphology (b) and significantly-enhanced production of IL-6 (c; p = 0.0016; paired t-test). (TIFF 3951 kb

Additional file 3: of Human central nervous system astrocytes support survival and activation of B cells: implications for MS pathogenesis

Figure S2. Effects of astrocytes cytokine neutralization on B cell survival and activation. B cells from HC were either cultured alone, or with stimulated astrocyte conditioned-medium (ACM), or with ACM pre-treated with neutralizing antibodies to IL-6 (a, b; anti-IL6: aIL-6), IL-15 (c, d; anti-IL-15: aIL-15) or BAFF (e, f; anti-BAFF: aBAFF); or pre-treated with corresponding isotype control antibodies. After 2 days of culture B cell viability was assessed using ANNEXIN V and 7AAD staining, and CD86 expression was measured by flow cytometry (representative experiment). (TIFF 4226 kb