TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: Various pathways involved in the pathogenesis of sJIA have been identified through gene expression profiling in peripheral blood mononuclear cells (PBMC), but not in neutrophils. Since neutrophils are important in tissue damage during inflammation, and are elevated as part of the acute phase response, we hypothesised that neutrophil pathways could also be important in the pathogenesis of sJIA. We therefore studied the gene profile in both PBMC and neutrophils of sJIA patients treated with tocilizumab.', 'We studied the transcriptomes of peripheral blood mononuclear cells (PBMC) and neutrophils from eight paired samples obtained from 4 sJIA patients taken before and after treatment, selected on the basis that they achieved ACR90 responses within 12 weeks of therapy initiation with tocilizumab. RNA was extracted and gene expression profiling was performed using Affymetrix GeneChip Human Genome U133 Plus 2.0 microarray platform. A longitudinal analysis using paired t-test (p\u2009<\u20090.05 and FC\u2009≥\u20091.5) was applied to identify differentially expressed genes (DEGs) between the two time points followed by ingenuity pathway analysis. Gene Set Enrichment Analysis (GSEA) and quantitative real-time PCR were then performed to verify the microarray results.', 'Gene ontology analysis in neutrophils revealed that response to tocilizumab significantly altered genes regulating mitochondrial dysfunction and oxidative stress (p\u2009=\u20094.6E-05). This was independently verified with GSEA, by identifying a set of oxidative genes whose expression correlated with response to tocilizumab. In PBMC, treatment of sJIA with tocilizumab appeared to affect genes in Oncostatin M signalling and B cell pathways.\Question: Are mitochondrial and oxidative stress genes differentially expressed in neutrophils of sJIA patients treated with tocilizumab : a pilot microarray study?

SOLUTION: For the first time we demonstrate that neutrophils from sJIA patients responding to tocilizumab showed significantly different changes in gene expression. These data could highlight the importance of mitochondrial genes that modulate oxidative stress in the pathogenesis of sJIA.

PROBLEM: Context: Childhood sexual abuse (CSA) has been associated with alterations in brain morphology using region of interest analyses that have focused on stress-sensitive target regions. This study was designed to ascertain the effects on gray matter volume (GMV) of exposure to CSA in healthy young adult college students selected based on exposure history regardless of psychiatric outcome. Voxel-based morphometry (VBM) provided unbiased delineation of the most significantly affected brain regions.', 'High-resolution T1-weighted magnetic resonance imaging (MRI) datasets were obtained for 23 unmedicated female subjects with CSA and 14 healthy female control subjects of equivalent age and socioeconomic status with no history of trauma. Cortical surface-based analysis (FreeSurfer) was performed to verify VBM results.', 'Gray matter volume was reduced by 12.6% and 18.1% in right and left primary visual (V1) and visual association cortices of abused subjects. This reduction was directly related to duration of CSA before age 12. Gray matter volume of left and right V1 correlated with measure of visual memory (r = .353, p = .032 and r = .448, p = .005). Cortical surface-based analysis indicated that GMV of abused subjects was reduced in the left fusiform (p = .004), left middle occipital (p = .04), and right lingual (p = .002) gyri.\Question: Is childhood sexual abuse associated with reduced gray matter volume in visual cortex of young women?

SOLUTION: Early visual experience exerts a strong influence on the developing mammalian visual cortex. Present findings indicate that exposure to CSA may also affect the development of this region and are apparent even in a population of subjects who are sufficiently healthy to matriculate.

PROBLEM: Context: The aim of this study was to evaluate long-term allograft salvage rates of patients with steroid refractory allograft rejection after kidney transplantation and to identify factors indicating a successful outcome.', 'Fifty patients with continuing rejection after high-dose steroids were included in the study. Baseline immunosuppression was switched from cyclosporine to tacrolimus in all patients. Twenty patients additionally received OKT3 as antirejection therapy. Patients having received a cadaveric renal transplant in 1995, excluding patients with steroid resistant rejection, were chosen as a control cohort.', 'Patient survival rates were 96% (n = 48) and 90% (n = 45) and allograft survival rates were 66% (n = 33) and 62% (n = 31) after 5 and 7 years following steroid refractory renal allograft rejection. Graft survival within the control cohort was 73% after 5 years and 69% after 7 years. Creatinine clearance increased from 20 +/- 15 ml/min/1.73 m2 at the start of tacrolimus therapy to 37 +/- 29 ml/min/1.73 m2 and to 32 +/- 26 ml/min/1.73 m2 after 5 and 7 years. OKT3 treatment predicted successful rescue therapy (p = 0.005 and p = 0.04 after 5 and 7 years).\Question: Is oKT3 therapy in addition to tacrolimus associated with improved long-term function in patients with steroid refractory renal allograft rejection?

SOLUTION:
Our data indicate a reasonable graft survival in steroid refractory renal allograft rejection using tacrolimus. OKT3 treatment in addition to tacrolimus therapy may be beneficial for long-term allograft survival.