Two Broad Categories Overlapping With Rheumatoid Arthritis Observed in Synovial Biopsies from Patients With Juvenile Idiopathic Arthritis.

Objective: The objective is to characterize transcriptomic profiles and immune cell composition and distribution in juvenile idiopathic arthritis (JIA) synovial biopsies, assess for associations of these features with clinical parameters, and compare JIA and rheumatoid arthritis (RA) synovial features.

Methods: RNA sequencing (RNASeq) was performed on 24 samples, with pathway analysis and inference of relative abundance of immune cell subsets based on gene expression data. Two multiplex fluorescence immunohistochemistry (IHC) panels were performed on 28 samples (including 13 on which RNASeq was performed), staining for CD206 classical and CD206 nonclassical macrophages, and CD8 and CD4 T and B lymphocytes.

p16, a marker of cellular senescence, is associated with renal disease in the B6. mouse model of lupus.

Objectives: Despite treatment, one-third of patients with lupus nephritis (LN) show a decline in renal function. Prognostic markers of poor outcome as well as novel therapeutic targets are therefore highly sought. We showed that p16, a marker of cellular senescence, is observed in baseline kidney biopsies from patients with LN, and is associated with renal disease.

Disease activity drives transcriptomic heterogeneity in early untreated rheumatoid synovitis.

Objectives: Transcriptomic profiling of synovial tissue from patients with early, untreated rheumatoid arthritis (RA) was used to explore the ability of unbiased, data-driven approaches to define clinically relevant subgroups.

Methods: RNASeq was performed on 74 samples, with disease activity data collected at inclusion. Principal components analysis (PCA) and unsupervised clustering were used to define patient clusters based on expression of the most variable genes, followed by pathway analysis and inference of relative abundance of immune cell subsets.

High p16, a marker of cellular senescence, is associated with renal injury, impairment and outcome in lupus nephritis.

Objectives: Because a significant fraction of patients with lupus nephritis (LN) develops renal impairment, there is a need to better understand the mechanisms underlying disease progression. Here, we assessed for cellular senescence in the LN kidney, and its association with disease severity and outcome.

Methods: We enumerated the number of cells positive for p16 protein, a marker of cellular senescence, by immunohistochemistry followed by digital quantification, on renal biopsies from 40 patients with active LN.

Characterization of two new high-grade B-cell lymphoma cell lines with MYC and BCL2 rearrangements that are suitable for in vitro drug sensitivity studies.

High-grade B-cell lymphomas with MYC and BCL2 or BCL6 rearrangements are highly aggressive B-cell lymphomas called double-hit lymphomas (HGBL-DH). They are particularly refractory to standard treatments and carry a poor prognosis. Fragments of resected tumoral lymph nodes from two HGBL-DH patients were put in culture.

Intrarenal activation of adaptive immune effectors is associated with tubular damage and impaired renal function in lupus nephritis.

Objectives: Chronic renal impairment remains a feared complication of lupus nephritis (LN). The present work aimed at identifying mechanisms and markers of disease severity in renal tissue samples from patients with LN.

Methods: We performed high-throughput transcriptomic studies (Illumina HumanHT-12 v4 Expression BeadChip) on archived kidney biopsies from 32 patients with LN and eight controls (pretransplant donors).

Case Reports in Oncological Medicine Myoepithelioma: A New Rearrangement Involving the Locus in a Case of Multiple Bone and Soft Tissue Lesions.

We report a case of multiple myoepithelioma with synchronous bone and soft tissue tumors, associated with a new genomic alteration of the locus. The lesions occurred in the foot by presenting one lump in the plantar soft tissue, and three lesions were detected in the calcaneus and in the navicular bone. All tumors showed the double immunophenotype of epithelial markers and S100 protein expression.

Reevaluation of ATR signaling in primary resting chronic lymphocytic leukemia cells: evidence for pro-survival or pro-apoptotic function.

ATM, primarily activated by DNA double-strand breaks, and ATR, activated by single-stranded DNA, are master regulators of the cellular response to DNA damage. In primary chronic lymphocytic leukemia (CLL) cells, ATR signaling is considered to be switched off due to ATR downregulation. Here, we hypothesized that ATR, though expressed at low protein level, could play a role in primary resting CLL cells after genotoxic stress.

Alternative Lengthening of Telomeres is characterized by reduced compaction of telomeric chromatin.

Proper telomeric chromatin configuration is thought to be essential for telomere homeostasis and stability. Previous studies in mouse suggested that loss of heterochromatin marks at telomeres might favor onset of Alternative Lengthening of Telomeres (ALT) pathway, by promoting homologous recombination. However, analysis of chromatin status at human ALT telomeres has never been reported.

Cancer-linked satellite 2 DNA hypomethylation does not regulate Sat2 non-coding RNA expression and is initiated by heat shock pathway activation.

Epigenetic dysfunctions, including DNA methylation alterations, play major roles in cancer initiation and progression. Although it is well established that gene promoter demethylation activates transcription, it remains unclear whether hypomethylation of repetitive heterochromatin similarly affects expression of non-coding RNA from these loci. Understanding how repetitive non-coding RNAs are transcriptionally regulated is important given that their established upregulation by the heat shock (HS) pathway suggests important functions in cellular response to stress, possibly by promoting heterochromatin reconstruction.

Human telomerase represses ROS-dependent cellular responses to Tumor Necrosis Factor-α without affecting NF-κB activation.

In addition to its well-established role in telomere synthesis, telomerase exerts non-canonical functions that may promote cancer and stem cell survival, notably by lowering reactive oxygen species (ROS) levels and acting as transcriptional cofactor in Wnt-β-catenin signaling pathway. We investigated the impact of telomerase on ROS-dependent and -independent cellular responses to Tumor Necrosis Factor-α (TNF-α), a potent inducer of endogenous ROS production and activator of NF-κB signaling pathway. Strikingly, telomerase overexpression in normal human fibroblasts treated with TNF-α strongly repressed ROS-dependent activation of both ERK1/2 mitogen-activated protein kinases and cell death.

Human periostin gene expression in normal tissues, tumors and melanoma: evidences for periostin production by both stromal and melanoma cells.

Background: Recently, periostin (POSTN), a gene encoding a protein with similarity to the fasciclin family and involved in cell survival and angiogenesis, has emerged as a promising marker for tumor progression in various types of human cancers. There is some controversy regarding both POSTN expression levels and the nature of periostin-producing cells within tumors. In this study, we used quantitative RT-PCR to assess periostin gene expression in normal tissues, primary cell cultures, tumor tissues and tumor cell lines.

Validation of an ELISA-based screening assay for the detection of amphetamine, MDMA and MDA in blood and oral fluid.

The use of amphetamine and 'ecstasy' (MDMA) has increased exponentially in many European countries since the late nineties, leading to a rapid growth in the number of clinical and forensic analyses. Therefore, a rapid screening procedure for these substances in biological specimens has become an important part of routine toxicological analysis in forensic laboratories. The objective of this study was to evaluate the Cozart amphetamine enzyme-linked immunosorbent assay (ELISA) for the screening of plasma samples and oral fluid samples (collected with the Intercept device).