Biomedical subjects

Nora G Singer

Publications and source records attributed to Nora G Singer.

6 recordsLinked to original sources

PubMed2006

CD166 expression, characterization, and localization in salivary epithelium: implications for function during sialoadenitis.

CD166 is an Ig superfamily molecule that binds homotypically to itself and heterotypically to CD6. Interactions between CD6 and CD166 are important during immune development and in alloreactivity. CD166 is expressed at increased levels in selected cancers and in rheumatoid arthritis synovium. Knowledge that CD166 was expressed in normal human salivary epithelium led to these studies of CD166 and CD6 in diseased mouse salivary glands, that resemble pathology seen in the human disease, Sjögren's syndrome. We showed that in mouse salivary epithelium CD166 was expressed but that expression of CD166 did not necessarily predict its function. Recombinant soluble CD6-Ig bound to CD6 ligands (CD6L) on transformed and freshly isolated salivary epithelial cells. Cross-blocking studies showed that binding of CD6-Ig to salivary epithelium was in part dependent on CD166, but that CD6-Ig binding may also involve additional CD6L. Binding of CD6-Ig was sensitive to trypsin digestion but resistant to digestion by collagenase and sialidase. Anti-CD166 ab precipitated CD166 from salivary epithelium pre- and post-treatment with the pro-inflammatory cytokine IFN-gamma. In contrast CD6-Ig only precipitated CD166 from IFN-gamma treated cells. More extensive colocalization between CD166 and the actin cytoskeleton was observed in sialoadenitis epithelium compared to control. We conclude that during sialoadenitis, CD166 undergoes a gain of function, resulting in closer association with the actin cytoskeleton and increased capacity to bind CD6. We suggest that altered CD166 function may contribute to the pro-inflammatory milieu during sialoadenitis seen in Sjögren's syndrome.

Actins↗

PubMed2005

Critical care myopathy in a child.

Critical care myopathy (CCM) is an important, often unrecognized cause of weakness in the intensive care unit (ICU). We report a child who developed severe myopathy in the ICU. Our patient was newly diagnosed to have autoimmune hepatitis that may have predisposed her to toxicity from corticosteroids and neuromuscular-blocking agents, but she recovered her strength completely. Risk factors that may have predisposed this patient to CCM include underlying liver dysfunction, presence of acute lung injury, use of corticosteroids, and use of neuromuscular blockade. Given the apparent prevalence and underreporting of CCM in the ICU, it is important for rheumatology consultants to include this entity in their differential diagnosis of weakness in critically ill children and adults, and to recommend appropriate evaluation.

Adolescent↗

PubMed2004

Expression and characterization of a novel CD6 ligand in cells derived from joint and epithelial tissues.

CD6 is a T cell surface glycoprotein that plays an important role in interactions of thymocytes with thymic epithelial cells and in mature T cell interactions with selected nonprofessional tissue APCs. We describe a novel CD6 ligand (CD6L) 3A11 Ag that is distinct from the known CD6L (CD166). The 3A11 protein is expressed on cells derived from human thymus, skin, synovium, and cartilage, and its expression is enhanced by IFN-gamma. mAbs directed against the 3A11 Ag and CD166 exhibit distinct patterns of binding to a panel of cell lines. Confocal microscopy shows that both CD166 and the 3A11 Ag are expressed at the cell surface, and that these proteins colocalize. The 3A11 Ag has a molecular mass of 130 kDa and is immunoprecipitated using either mAb 3A11 or soluble CD6-Ig fusion protein. mAbs directed against individual CD6L were less potent than was soluble CD6-Ig fusion protein in reducing adhesion of T cells to adherent 3A11-positive epithelial cells in vitro, suggesting that these Abs recognize epitopes on the 3A11 Ag and CD166 that are distinct from CD6 binding sites. Finally, transfection of epithelial cells with CD166-specific small interfering RNAs significantly decreased CD166 expression without alteration in 3A11 Ag levels, and thus confirmed that these two CD6L are distinct. Taken together, our data identifies a novel 130-kDa CD6L that may mediate interactions of synovial and epithelial cells with T lymphocytes.

Activated-Leukocyte Cell Adhesion Molecule↗

PubMed2004

Remittive agents in pediatric rheumatology.

PURPOSE OF REVIEW: Children with rheumatic diseases frequently require therapy with disease-modifying antirheumatic drugs and/or biologic agents. Therapies that have been prospectively tested in adults are often used in children before full evaluation of their safety and efficacy. Published experience that may report "off-label" usage can be helpful in decision making, although such reports do not reduce the need for prospective clinical trials in children. The purpose of this review is to summarize the recent published evidence regarding efficacy (and safety, when available) of standard and novel agents used in pediatric rheumatic disease. RECENT FINDINGS: Etanercept, one of three currently available tumor necrosis factor-alpha inhibitors has a juvenile idiopathic arthritis indication. Novel "off-label" uses in children for interleukin-1 receptor agonist (Anakinra), antiinterleukin-6 receptor antibody (MRA), and rituximab (anti-CD20 monoclonal antibody) are discussed. SUMMARY: This review summarizes the published evidence that supports the use of selected disease-modifying antirheumatic drugs and novel biologic agents in children with rheumatic diseases.

Adolescent↗

PubMed2004

Juvenile idiopathic arthritis: parent-child discrepancy on reports of pain and disability.

OBJECTIVE: To examine the incidence and nature of disagreements about pain and functional disability between parents and their children with juvenile idiopathic arthritis (JIA) and to identify demographic and psychosocial predictors of parent-child disagreement about pain and functional disability. METHODS: Participants comprised 63 children 8-16 years of age (mean 12.36 +/- 2.61) and their parents, followed as part of a longitudinal study of pain in children. During routine rheumatology clinic visits, children and their parents completed validated measures of pain, depressive symptoms, and functional disability. RESULTS: Parents and children often disagreed as to the frequency and intensity of pain and to the degree of disability caused by arthritis. Child depressive symptoms (p < 0.01) and parental perceptions of child limitations (p < 0.02) predicted parent-child disagreement about the frequency of the child's pain. Parental perceptions of child limitations also predicted parent-child disagreement about the child's level of functional disability (p < 0.04). Those children who estimated their level of disability to be different than their parents' rating also were more depressed compared to children who agreed with their parents about their level of disability (p < 0.01). CONCLUSION: Discrepancy between parent and child reports of pain and disability in children with JIA is common. Findings suggest that such disagreements in reporting of pain and functional disability by parents and their children with JIA are associated with underlying depressive symptoms in children.

Activities of Daily Living↗

PubMed2002

CD6: expression during development, apoptosis and selection of human and mouse thymocytes.

CD6, a 130-kDa surface glycoprotein, is expressed primarily on cells of T lineage. A co-stimulatory role for CD6 in mature T cells has been shown, but the function of CD6 during thymocyte development is unknown. Since CD6 ligands are expressed on thymic epithelium, their interactions with CD6 could be important in thymic selection. In this report we show that CD6 is developmentally regulated in human and mouse thymocytes, and further demonstrate that increase in the level of CD6 expression correlates with expression of the selection marker CD69. We also show that activation via CD2 induces CD6 expression on mature human thymocytes and on a subset of immature human thymocytes that are resistant to apoptosis. In human and mouse thymocytes that express heterogeneous TCR, CD6 increases occur as double-positive thymocytes are selected to a single-positive stage. In contrast, in thymocytes from TCR transgenic mice, CD6 is barely increased following selection, suggesting that as functional avidity increases, requirements for CD6-dependent co-stimulation decrease. Taken together, these results indicate that during thymic development CD6-dependent signals may contribute both to thymocyte survival, and to the overall functional avidity of selection in both man and mouse.

Animals↗