Influence of lipopolysaccharide on proinflammatory gene expression in human corneal, conjunctival and meibomian gland epithelial cells

PURPOSE: Lipopolysaccharide (LPS), a bacterial endotoxin, is known to stimulate leuokotriene B4 (LTB4) secretion by human corneal (HCECs), conjunctival (HConjECs) and meibomian gland (HMGECs) epithelial cells. We hypothesize that this LTB4 effect represents an overall induction of proinflammatory gene expression in these cells. Our objective was to test this hypothesis. METHODS: Immortalized HCECs, HConjECs and HMGECs were cultured in the presence or absence of LPS (15 μg/ml) and ligand binding protein (LBP; 150 ng/ml). Cells were then processed for RNA isolation and the analysis of gene expression by using Illumina BeadChips, background subtraction, cubic spline normalization and GeneSifter software. RESULTS: Our findings show that LPS induces a striking increase in proinflammatory gene expression in HCECs and HConjECs. These cellular reactions are associated with a significant up-regulation of genes associated with inflammatory and immune responses (e.g. IL-1β, IL-8, and tumor necrosis factor), including those related to chemokine and Toll-like receptor signaling pathways, cytokine-cytokine receptor interactions, and chemotaxis. In contrast, with the exception of Toll-like signaling and associated innate immunity pathways, almost no proinflammatory ontologies were upregulated by LPS in HMGECs. CONCLUSIONS: Our results support our hypothesis that LPS stimulates proinflammatory gene expression in HCECs and HConjECs. However, our findings also show that LPS does not elicit such proinflammatory responses in HMGECs

Testosterone Influence on Gene Expression in Lacrimal Glands of Mouse Models of Sjögren Syndrome

Purpose: Sjögren syndrome is an autoimmune disorder that occurs almost exclusively in women and is associated with extensive inflammation in lacrimal tissue, an immune-mediated destruction and/or dysfunction of glandular epithelial cells, and a significant decrease in aqueous tear secretion. We discovered that androgens suppress the inflammation in, and enhance the function of, lacrimal glands in female mouse models (e.g., MRL/MpJ-Tnfrsf6lpr [MRL/lpr]) of Sjögren syndrome. In contrast, others have reported that androgens induce an anomalous immunopathology in lacrimal glands of nonobese diabetic/LtJ (NOD) mice. We tested our hypothesis that these hormone actions reflect unique, strain- and tissue-specific effects, which involve significant changes in the expression of immune-related glandular genes. Methods: Lacrimal glands were obtained from age-matched, adult, female MRL/lpr and NOD mice after treatment with vehicle or testosterone for up to 3 weeks. Tissues were processed for analysis of differentially expressed mRNAs using CodeLink Bioarrays and Affymetrix GeneChips. Data were analyzed with bioinformatics and statistical software. Results: Testosterone significantly influenced the expression of numerous immune-related genes, ontologies, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in lacrimal glands of MRL/lpr and NOD mice. The nature of this hormone-induced immune response was dependent upon the autoimmune strain, and was not duplicated within lacrimal tissues of nonautoimmune BALB/c mice. The majority of immune-response genes regulated by testosterone were of the inflammatory type. Conclusions: Our findings support our hypothesis and indicate a major role for the lacrimal gland microenvironment in mediating androgen effects on immune gene expression

Quantum teleportation with nonclassical correlated states in noninertial frames

Quantum teleportation is studied in noninertial frame, for fermionic case, when Alice and Bob share a general nonclassical correlated state. In noninertial frames two fidelities of teleportation are given. It is found that the average fidelity of teleportation from a separable and nonclassical correlated state is increasing with the amount of nonclassical correlation of the state. However, for any particular nonclassical correlated state, the fidelity of teleportation decreases by increasing the acceleration.Comment: 10 pages, 3 figures, expanded version to appear in Quantum Inf. Proces

Dihydrotestosterone suppression of proinflammatory gene expression in human meibomian gland epithelial cells

Purpose: We discovered that dihydrotestosterone (DHT) decreases the ability of lipopolysaccharide, a bacterial toxin, to stimulate the secretion of leukotriene B4, a potent proinflammatory mediator, by immortalized human meibomian gland epithelial cells (IHMGECs). We hypothesize that this hormone action reflects an androgen suppression of proinflammatory gene activity in these cells. Our goal was to test this hypothesis. For comparison, we also examined whether DHT treatment elicits the same effect in immortalized human corneal (IHC) and conjunctival (IHConj) ECs. Methods: Differentiated cells were cultured in media containing vehicle or 10 nM DHT. Cells (n = 3 wells/treatment group) were then processed for RNA isolation and the analysis of gene expression by using Illumina BeadChips, background subtraction, cubic spline normalization and Geospiza software. Results: Our results demonstrate that DHT significantly suppressed the expression of numerous immune-related genes in HMGECs, such as those associated with antigen processing and presentation, innate and adaptive immune responses, chemotaxis, and cytokine production. DHT also enhanced the expression of genes for defensin β1, IL-1 receptor antagonist, and the anti-inflammatory serine peptidase inhibitor, Kazal type 5. In contrast, DHT had no effect on proinflammatory gene expression in HCECs, and significantly increased 33 gene ontologies linked to the immune system in HConjECs. Conclusions: Our findings support our hypothesis that androgens suppress proinflammatory gene expression in IHMGECs. This hormone effect may contribute to the typical absence of inflammation within the human meibomian gland

Overgeneral Memory Retrieval an Ineffective Problem-Solving in Depressed Patients with Suicidal Ideation: implications for Therapy

The present study was designed to extend our knowledge around cognitive aspects of memory retrieval and problem-solving in two groups of clinically depressed patients. We administered an autobiographical memory test, a means-ends problem-solving task, Beck Depression Inventory, and Beck Hopelessness Scale to measure respectively level of specificity in memory retrieval, problem-solving effectiveness, depression and hopelessness in clinically depressed patients with suicidal ideation and in a matched control group of depressed patients without suicide ideation. Both groups met DSM-IV criteria for major depression disorder without psychotic features. The depressed suicide-ideators were significantly more hopeless than their non-ideator counterparts. Also an overall tendency was found for the ideator group to retrieve less specific memories compared to the non-ideator group. Depressed patients’ bias toward negative memory retrieval is broadly documented. Access to non-specific memories in depressed people can lead to ineffective problem solutions and subsequently hopelessness. By this account, this very vicious cycle continues over time to resonate powerfully, perhaps leading to suicidal attempt. An emergence of suicidal ideation when assessing helps clinicians identify those who are most at risk for suicide. They can be targeted then for intensive therapy designed to lower the risk.El presente estudio se diseñó con el propósito de ampliar el conocimiento acerca de los aspectos cognifivos de la recuperación de memoria y la solución de problemas en dos grupos de pacientes con depresión: pacientes con ideación suicida y pacientes sin ideación suicida. Ambos grupos cumplían los criterios DSM-IV para el trastorno de depresión mayor sin características psicóticas. Se administraron a los participantes una prueba de memoria autobiográfica, una tarea de solución de problemas, el Inventario de Depresión y la Escala de Desesperanza de Beck, para medir el nivel de especificidad en la recuperación de recuerdos, la efectividad en solución de problemas, depression and hopelessness. Los ideadores suicidas puntuaron significativamente más alto en desesperanza que los no ideadores. Se encontró una tendencia global en el grupo de ideadores a recuperar menos memorias específicas en comparación con los no ideadores. Se discuten los resultados de acuerdo al conocido sesgo en la recuperación de memorias negativas en pacientrs depresivos y la emergencia de la ideación suicida como identificador de riesgo para el suicidio.

Does estrogen deficiency cause lacrimal gland inflammation and aqueous-deficient dry eye in mice?

Abstract not availableRaheleh Rahimi Darabad, Tomo Suzuki, Stephen M. Richards, Frederick A. Jakobiec, Fouad R. Zakka, Stefano Barabino, David A. Sulliva

Influence of aromatase absence on the gene expression and histology of the mouse meibomian gland

Purpose.: We hypothesize that aromatase, an enzyme that controls estrogen biosynthesis, plays a major role in the sex-related differences of the meibomian gland. To begin to test this hypothesis, we examined the influence of aromatase absence, which completely eliminates estrogen production, on glandular gene expression and histology in male and female mice. Methods.: Meibomian glands were obtained from adult, age-matched wild-type (WT) and aromatase knockout (ArKO) mice. Tissues were processed for histology or the isolation of total RNA, which was analyzed for differentially expressed mRNAs by using microarrays. Results.: Our results show that aromatase significantly influences the expression of more than a thousand genes in the meibomian gland. The nature of this effect is primarily sex-dependent. In addition, the influence of aromatase on sex-related differences in gene expression is predominantly genotype-specific. However, many of the sex-related variations in biological process, molecular function, and cellular component ontologies, as well as in KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, are remarkably similar between WT and ArKO mice. The loss of aromatase activity has no obvious effect on the histology of meibomian glands in male or female mice. Conclusions.: Our findings demonstrate that aromatase has a significant impact on gene expression in the meibomian gland. The nature of this influence is sex-dependent and genotype-specific; however, many of the sex-related variations in gene ontologies and KEGG pathways are similar between WT and ArKO mice. Consequently, it appears that aromatase, and by extension estrogen, do not play a major role in the sex-related differences of the mouse meibomian gland.Raheleh Rahimi Darabad, Tomo Suzuki, Stephen M. Richards, Roderick V. Jensen, Frederick A. Jakobiec, Fouad R. Zakka, Shaohui Liu and David A. Sulliva

Sex Effects on Gene Expression in Lacrimal Glands of Mouse Models of Sjögren Syndrome

Purpose: Sjögren syndrome is an autoimmune disease that occurs primarily in women, and is associated with lacrimal gland inflammation and aqueous-deficient dry eye. We hypothesize that sex-associated differences in lacrimal gland gene expression are very important in promoting lymphocyte accumulation in this tissue and contribute to the onset, progression, and/or severity of the inflammatory disease process. To test our hypothesis, we explored the nature and extent of sex-related differences in gene expression in autoimmune lacrimal glands. Methods: Lacrimal glands were collected from age-matched, adult, male and female MRL/MpJ-Tnfrsf6lpr (MRL/lpr) and nonobese diabetic/LtJ (NOD) mice. Glands were processed for the analysis of differentially expressed mRNAs by using CodeLink Bioarrays and Affymetrix GeneChips. Data were evaluated with bioinformatics and statistical software. Results: Our results show that sex significantly influences the expression of thousands of genes in lacrimal glands of MRL/lpr and NOD mice. The immune nature of this glandular response is very dependent on the Sjögren syndrome model. Lacrimal glands of female, as compared with male, MRL/lpr mice contain a significant increase in the expression of genes related to inflammatory responses, antigen processing, and chemokine pathways. In contrast, it is the lacrimal tissue of NOD males, and not females, that presents with a significantly greater expression of immune-related genes. Conclusions: These data support our hypothesis that sex-related differences in gene expression contribute to lacrimal gland disease in Sjögren syndrome. Our findings also suggest that factors in the lacrimal gland microenvironment are critically important in mediating these sex-associated immune effects

Discontinuity of Chronic Medications in Patients Discharged from the Intensive Care Unit

BACKGROUND: Intensive care unit (ICU) admission may connote an elevated risk of unintentional chronic medication discontinuation because of its focus on acute illnesses and the multiple care transitions. OBJECTIVE: To determine the proportion of patients discharged from the ICU whose previously prescribed chronic medications were unintentionally discontinued during their hospitalization. DESIGN AND PARTICIPANTS: Hospital records of consecutive ICU discharges at 1 academic and 2 community hospitals in Toronto, Canada, throughout 2002 were reviewed. Eligible patients were prescribed at least 1 of 6 medication groups before hospitalization: (1) HMG co-A reductase inhibitors (statins); (2) antiplatelets/anticoagulants (aspirin, clopidogrel, ticlopidine, warfarin); (3) l-thyroxine; (4) non-prn inhalers (anticholinergic, β-agonist, or steroid); (5) acid-suppressing drugs (H2 antagonists and proton pump inhibitors); and (6) allopurinol. MEASUREMENTS: Use of explicit criteria to assess the proportion of patients whose previously prescribed chronic medications were unintentionally discontinued at hospital discharge. RESULTS: A total of 1,402 charts were eligible for the study and 834 had prescriptions for at least 1 of the medication groups. Thirty-three percent (251/834) of patients had 1 or more of their chronic medications omitted at hospital discharge. Multivariable logistic regression analysis found that patients from the academic hospital (adjusted odds ratio [OR]=0.70, 95% confidence interval [CI] 0.49 to 1.0) and those with medical diagnoses (adjusted OR=0.48, 95% CI 0.31 to 0.75) had a decreased risk for chronic medication discontinuation. CONCLUSIONS: Patients discharged from the ICU often leave the hospital without note of their previously prescribed chronic medications. Careful review of medication lists at ICU discharge could avoid potential adverse outcomes related to unintentional discontinuation of chronic medications at hospital discharge