Biomedical subjects

Sandra C Christiansen

Publications and source records attributed to Sandra C Christiansen.

5 recordsLinked to original sources

PubMed2003

Bradykinin increases the in vivo expression of the CXC chemokine receptors CXCR1 and CXCR2 in patients with allergic rhinitis.

BACKGROUND: Increased levels of bradykinin and IL-8 have been detected within the airways of individuals with active symptoms of allergic rhinitis and asthma. OBJECTIVE: We sought to investigate the in vivo effect of bradykinin on the expression of the IL-8 receptors CXCR1 and CXCR2 in nasal cells. METHODS: Nasal samples were obtained from patients with active allergic rhinitis; patients with mild, quiescent allergic rhinitis; and healthy control subjects. CXCR1 and CXCR2 mRNA expression in the nasal cells was measured by means of quantitative real-time RT-PCR in baseline samples from all subjects, as well as in samples obtained after in vivo bradykinin challenge in healthy control subjects and patients with mild allergic rhinitis. CXCR1 and CXCR2 cell-surface expression was also assessed by means of flow cytometry in nasal epithelial cells at baseline and after ex vivo bradykinin challenge. RESULTS: No difference was seen in CXCR1 or CXCR2 mRNA expression between healthy control subjects and patients with quiescent allergic rhinitis at baseline; however, patients with active allergic rhinitis had increased baseline expression of both CXCR1 and CXCR2 mRNA. In vivo nasal bradykinin challenge significantly increased CXCR1 and CXCR2 mRNA expression in patients with quiescent allergic rhinitis but had no effect in healthy control subjects. Low levels of CXCR1 but not CXCR2 cell-surface expression was detected in nasal epithelial cells at baseline, and ex vivo bradykinin challenge induced CXCR2 cell-surface expression in nasal epithelial cells from patients with mild allergic rhinitis. CONCLUSION: This study demonstrates the in vivo regulation of chemokine receptors by means of bradykinin in human airway tissue in patients with allergic rhinitis.

Bradykinin↗

PubMed2002

Functional expression of the C-X-C chemokine receptor CXCR4 by human bronchial epithelial cells: regulation by proinflammatory mediators.

CXCR4 and its ligand stromal cell-derived factor 1alpha (SDF-1alpha) have recently been implicated in the development of airway inflammation in a mouse model of allergic airway disease. Here we report, for the first time, the expression of a functional CXCR4 in primary human normal bronchial epithelial cells and the regulation of CXCR4 gene expression by proinflammatory mediators. Both bradykinin (BK) and IL-1beta induced an accumulation of CXCR4 mRNA in normal bronchial epithelial cells in a time-dependent manner, with peak levels of CXCR4 mRNA reached between 4 and 24 h after stimulation. Ligand activation of CXCR4 in airway epithelial cells resulted in the activation of the extracellular signal-regulated kinase and stress-activated protein kinase/c-Jun amino-terminal kinase signaling pathways and calcium mobilization. Pretreatment of airway epithelial cells with BK or IL-1beta enhanced SDF-1alpha induced phospho-extracellular signal-regulated kinase and calcium mobilization, in addition to increasing the level of CXCR4 protein. Finally, we describe the expression of CXCR4 mRNA and its regulation by BK in vivo in human nasal tissue. CXCR4 mRNA levels are significantly higher in the nasal tissue of symptomatic allergic rhinitis subjects compared with normal subjects. Moreover, BK challenge significantly increased CXCR4 mRNA levels in nasal tissue of mild allergic rhinitis subjects in vivo, but not normal controls. In conclusion, this study demonstrates that human airway epithelial cells respond to proinflammatory mediators by up-regulating the chemokine receptor CXCR4, thus enabling the cells to respond more effectively to constitutively expressed SDF-1alpha. This may lead to enhanced activation of intracellular signaling pathways resulting in the release of mediators involved in inflammatory allergic airway disease.

Bradykinin↗

PubMed2002

Up-regulation of functional kinin B1 receptors in allergic airway inflammation.

B1 receptors are known to be induced during allergic airway inflammation in animal models. However, little is known regarding in vivo B1 receptor expression in humans. We examined B1 receptor mRNA expression in nasal tissue samples from allergic rhinitis and normal subjects. Allergic rhinitis subjects displayed significantly higher expression of B1 receptor mRNA than did the normal subjects, and nasal allergen challenge increased B1 receptor mRNA expression at 8 to 24 h time points in allergic rhinitis subjects. No significant difference was found in B2 receptor expression. To confirm B2 and B1 receptor functional activity, subjects were challenged with kinin agonists. Nasal challenge with the B1 receptor ligand, Lys-des-Arg-bradykinin (BK), activated extracellular signal-regulated kinase in allergic rhinitis, but not normal, subjects. Nasal challenge with the B2 receptor ligand, BK, activated extracellular signal-regulated kinase in both allergic rhinitis and normal subjects. The consequences of B1 receptor activation were investigated using the human airway epithelial cell lines A549 and BEAS-2B. We demonstrated that Lys-des-Arg-BK activates the transcription factor AP-1. Taken together, these results show that functional B1 receptors are induced in the airway during allergic inflammation and suggest that they participate in the regulation of gene expression.

Adult↗

PubMed2002

Serving the underserved: school-based asthma intervention programs.

Asthma is a common and costly disease, which disproportionately affects young, ethnic minority, and impoverished individuals. A heightened public awareness has catalyzed a variety of efforts to reduce the impact of childhood asthma in the United States. Despite these efforts, however, at-risk groups continue to suffer excess morbidity. Strategies are required that can specifically address the needs of underserved communities. We review the underlying rationale and progress of school-based programs designed to assist asthmatic children.

Asthma↗

PubMed2002

Health care consumption among elderly patients in california: a comprehensive 10-year evaluation of trends in hospitalization rates and charges.

PURPOSE: This report examines health care rates, charges, and patterns of consumption from a comprehensive California hospitalization data set covering 1986-1995. An improved understanding of current trends in health care consumption would facilitate the development of future resource allocation models. DESIGN AND METHODS: We obtained discharge and charge data from all licensed nonfederal hospitals in California between 1986 and 1995 relating to inpatient discharges of individuals aged 55 years and older. We used the direct method of standardization to adjust discharge statistics for differing age and gender case mixes, and we adjusted all charges to 1990 dollars for cost comparisons. RESULTS: Standardized to the 1990 population, annual discharge rates declined between 1986 and 1992, then leveled off to about 227 per 1,000 between 1993 and 1995. Rates of both discharges and charges for men consistently exceeded those for women, there being about a 5-year lag between female and male rates of discharge. The insurance payer mix shifted between 1986 and 1995, with dramatic declines in private insurance mirrored by increases in managed care. IMPLICATIONS: Hospital care consumption among the elderly people in California demonstrates a trend of increasing adjusted total charges despite declining hospitalization rates. Overall, individuals aged 55 years and older comprise 18% of the California population and incur 52% of discounted total charges. Private insurance has virtually disappeared, replaced by HMO/PHP/PPO organizations; still, charges to governmental sources (primarily Medicare and Medi-Cal) account for about 78% of total billings. Absolute numbers of Californians aged 55 and older are projected to increase 54% by 2010 and 226% by 2025 compared with 1995, engendering a dramatic increase in the financial burden of health care to this segment of the population.

Aged↗