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1.
J Allergy Clin Immunol ; 131(2): 395-404, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23374267

ABSTRACT

BACKGROUND: Rhinovirus infection is a leading cause of exacerbation of airway diseases. We hypothesize that airway viruses activate inflammatory cells, inducing airway dysfunction. We have previously shown that airway viruses can induce eosinophil degranulation when cocultured with T cells and monocyte-derived dendritic cells (moDCs). These findings suggested that antigen presentation was important for T-cell activation. OBJECTIVE: Given the clinical importance of rhinovirus, we sought to determine whether it had any unique abilities to activate inflammatory cells compared with another common virus, such as respiratory syncytial virus (RSV). METHODS: We cocultured combinations of human leukocytes (T cells, moDCs, and eosinophils) with each virus. Using assays of BrdU incorporation, flow cytometry, and ELISA, we measured T-cell activation, rhinovirus expression, T-cell death, and eosinophil cysteinyl leukotriene release. RESULTS: In contrast to RSV, rhinovirus induced T-cell activation without the involvement of moDCs. Without moDCs, rhinovirus induced T-cell proliferation of both CD4 and CD8(+) cells, cytokine production, and ultimately, eosinophil stimulation. Although chloroquine inhibited RSV-induced activation of T cells through moDCs, rhinovirus was not inhibited; UV inactivation did block the rhinovirus effect. We also found that T cells could be infected by rhinovirus in vitro and within human nasal explant tissue. Although Toll-like receptors did not appear to be involved in T-cell activation, antagonists of Jun N-terminal kinase and nuclear factor κB did inhibit T-cell responses to rhinovirus. CONCLUSION: Rhinovirus has the unique ability to bypass antigen presentation and directly infect and activate human T cells. This could explain the strong association of rhinovirus with exacerbation of airway diseases.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Picornaviridae Infections/immunology , Rhinovirus/immunology , Antigen Presentation/immunology , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/virology , Cell Death/immunology , Cell Growth Processes/immunology , Cytokines/immunology , Dendritic Cells/immunology , Eosinophils/immunology , Eosinophils/virology , Genes, MHC Class II/immunology , Humans , Inflammation/immunology , Inflammation/virology , JNK Mitogen-Activated Protein Kinases/immunology , Leukotrienes/immunology , Lymphocyte Activation/immunology , Monocytes/immunology , NF-kappa B/immunology , Picornaviridae Infections/virology , Respiratory Syncytial Viruses/immunology , Respiratory Tract Diseases/immunology , Respiratory Tract Diseases/virology , Toll-Like Receptors/immunology
2.
J Pediatr Endocrinol Metab ; 26(5-6): 587-9, 2013.
Article in English | MEDLINE | ID: mdl-23443264

ABSTRACT

We report on a patient who initially presented with delayed puberty and an absent uterus on imaging with ultrasound and MRI. She was subsequently diagnosed with Turner Syndrome. Turner Syndrome typically presents with early loss of ovarian function and should be considered when primary ovarian insufficiency is present with apparent absent uterus on imaging. Follow-up imaging of the apparent absent uterus post-estrogen replacement therapy is important to confirm a normal uterus. A diagnosis of an absent uterus can be psychologically traumatic for patients and families, and can have significant implications for future fertility options.


Subject(s)
Primary Ovarian Insufficiency/genetics , Primary Ovarian Insufficiency/pathology , Turner Syndrome/genetics , Turner Syndrome/pathology , Uterus/abnormalities , Adolescent , Female , Humans
3.
J Allergy Clin Immunol ; 127(3): 757-64.e1-6, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21377043

ABSTRACT

BACKGROUND: The ability to diagnose and monitor asthma on the basis of noninvasive measurements of airway cellular dysfunction is difficult in the typical clinical setting. OBJECTIVE: Metabolomics is the study of molecules created by cellular metabolic pathways. We hypothesized that the metabolic activity of children with asthma would differ from healthy children without asthma. Furthermore, children having an asthma exacerbation would be different compared with children with stable asthma in outpatient clinics. Finally, we hypothesized that (1)H-nuclear magnetic resonance (NMR) would measure such differences using urine samples, one of the least invasive forms of biofluid sampling. METHODS: Children (135 total, ages 4-16 years) were enrolled, having met the criteria of healthy controls (C), stable asthma in the outpatient clinic (AO), or unstable asthma in the emergency department (AED). Partial least squares discriminant analysis was performed on the NMR data to create models of separation (70 metabolites were measured/urine sample). Some NMR data were withheld from modeling to be run blindly to determine possible diagnostic accuracy. RESULTS: On the basis of the model of AO versus C, 31 of 33 AO samples were correctly diagnosed with asthma (94% accuracy). Only 1 of 20 C samples was incorrectly labeled as asthma (5% misclassification). On the basis of the AO versus AED model, 31 of the 33 AO samples were correctly diagnosed as outpatient asthma (94% accurate). CONCLUSION: This is the first report suggesting that (1)H-NMR analysis of human urine samples has the potential to be a useful clinical tool for physicians treating asthma.


Subject(s)
Asthma/urine , Biomarkers/urine , Magnetic Resonance Spectroscopy , Metabolomics , Adolescent , Asthma/diagnosis , Case-Control Studies , Child , Child, Preschool , Female , Humans , Male , Predictive Value of Tests , Sensitivity and Specificity
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