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Biomedical subjects

David Creery

Publications and source records attributed to David Creery.

16 recordsLinked to original sources

Differential regulation of CXCR4 and CCR5 expression by interleukin (IL)-4 and IL-13 is associated with inhibition of chemotaxis and human immunodeficiency Virus (HIV) type 1 replication but not HIV entry into human monocytes.

Chemokine receptors CXCR4 and CCR5 play a key role in Human Immunodeficiency Virus (HIV) entry into CD4+ monocytic cells. Alteration in the expression levels of these receptors by immunoregulatory cytokines may influence viral entry and hence susceptibility to HIV infection, viral tropism, and disease progression. Helper T cell type 2 (Th2) cytokines interleukin (IL)-4 and IL-13, which share a subunit of their receptor components and exhibit similar biological effects, have been shown to play a key role in HIV infection and disease progression. In this study, we investigated the effects of IL-4 and IL-13 on the expression of CXCR4 and CCR5, and the biological implications of alteration of CXCR4 and CCR5 regulation on monocytic cells with respect to their migration in response to chemokines, HIV entry, and its replication. The results suggest that both IL-4 and IL-13 inhibited the expression of CXCR4, in contrast to CCR5, which was inhibited by IL-13 alone. The downregulation of CXCR4 and CCR5 was correspondingly associated with the inhibition of their respective ligand-induced chemotaxis. Although IL-13 inhibited the expression of both CXCR4 and CCR5, this downregulation of chemokine receptor expression was not sufficient to prevent virus entry. Furthermore, both IL-4 and IL-13 inhibited viral replication in monocytic cells, suggesting that inhibition of chemokine receptor expression per se by these cytokines may not be sufficient to prevent virus entry, and indicating these cytokines may be inhibiting viral replication by targeting pathways subsequent to virus entry.

Chemotaxis, Leukocyte↗

Noninvasive therapy with helium-oxygen for severe bronchiolitis.

OBJECTIVE: To determine whether noninvasive therapy using a helium-oxygen mixture reduces the use of positive-pressure ventilation in the treatment of respiratory failure caused by severe bronchiolitis. STUDY DESIGN: This was a multicenter, randomized, double-blind, placebo-controlled trial that recruited infants in 4 pediatric intensive care units (PICUs). A total of 39 nonintubated infants with severe bronchiolitis caused by respiratory syncytial virus (RSV) were randomly assigned within 8 hours of PICU admission to receive a helium-oxygen mixture (helium group) or an air-oxygen mixture (control group) through an inflatable head hood. The primary study outcome was the requirement for positive pressure mechanical ventilation. Results were compared using Fisher's exact test. RESULTS: No differences were noted between the control and helium groups with respect to age (1.0 vs 1.1 months), prematurity, or family history of asthma or smoking. Positive pressure ventilation was judged necessary for 4 of the 21 (19.0%) infants in the control group and in 4 of the 18 (22.2%) in the helium group (relative risk = 1.17; 95% confidence interval = 0.34 to 4.01). CONCLUSIONS: This study did not detect any differences between the patients in the helium group and the control group with respect to the rate of positive-pressure ventilation.

Bronchiolitis, Viral↗

Costs associated with infant bronchiolitis in the Baffin region of Nunavut.

UNLABELLED: OBJECTIVE. Although infants living in the north of Canada have been reported to have one of the highest rates of hospital admission for bronchiolitis in the world, the economic effects of this condition have not been reported. Passive immunization against the Respiratory Syncytial Virus, the most common causative agent of infant bronchiolitis, is available. METHODS: We tabulated transportation, in-hospital care and family accommodation costs for infants of less than 12 months of age residing in the Baffin Region of Nunavut aged who were admitted to Baffin Regional Hospital in Iqaluit, Nunavut, and the Children's Hospital of Eastern Ontario in Ottawa, Ontario, with a primary diagnosis of bronchiolitis or viral pneumonia, over a 36-month period, between April 1999 and March 2002. RESULTS: One hundred fifty-nine infants were admitted a total of 210 times, with 196 admissions to Baffin Regional Hospital, and 14 to the Children's Hospital of Eastern Ontario, during the study period. The overall, annual, population-based admission rate for the Baffin Region of Nunavut was 197 admissions per thousand infants per year. Total costs were $2,997,373 ($2,357,747 for Baffin Regional Hospital, $639,625 for the Children's Hospital of Eastern Ontario). Overall average costs were $14,273 per admission, $12,029 for infants admitted to Baffin Regional Hospital and $45,688 for infants admitted to the Children's Hospital of Eastern Ontario. CONCLUSIONS: Infant bronchiolitis in the Baffin Region of Nunavut represents a significant burden on the territorial health care system.

Bronchiolitis, Viral↗

Nef protein of human immunodeficiency virus and lipopolysaccharide induce expression of CD14 on human monocytes through differential utilization of interleukin-10.

We investigated the expression of membrane-bound CD14 (mCD14) on monocytes and soluble CD14 (sCD14) released into the culture supernatants of peripheral blood lymphocytes (PBMC) from human immunodeficiency virus (HIV)-infected individuals. Monocytes from HIV-positive individuals exhibited both enhanced mCD14 expression and sCD14 production in the PBMC culture supernatants compared to the levels of mCD14 and sCD14 in HIV-negative individuals. This enhanced mCD14 expression and sCD14 production in HIV-infected individuals may be due to the effects of cytokines, the bacterial product lipopolysaccharide (LPS), and/or the HIV regulatory antigens Tat and Nef. Interleukin-10 (IL-10), an immunoregulatory cytokine, as well as LPS enhanced mCD14 expression and the release of sCD14 in the culture supernatants. HIV-Nef, unlike Tat, enhanced mCD14 expression on monocytes but did not induce the release of sCD14 into the culture supernatants. Studies conducted to investigate the mechanism underlying HIV-Nef-induced mCD14 expression revealed that HIV-Nef upregulated mCD14 expression via a mechanism that does not involve endogenously produced IL-10. In contrast, LPS upregulated the expression of mCD14 and increased the release of sCD14 via a mechanism that involves, at least in part, endogenously produced IL-10. Furthermore, dexamethasone, an anti-inflammatory and immunosuppressive agent, inhibited HIV-Nef-induced CD14 expression in an IL-10-independent manner. In contrast, dexamethasone inhibited IL-10-dependent LPS-induced CD14 expression by interfering with IL-10-induced signals but not by blocking IL-10 production. These results suggest that HIV-Nef and IL-10 constitute biologically important modulators of CD14 expression which may influence immunobiological responses to bacterial infections in HIV disease.

Adult↗