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Biomedical subjects

L O'Neill

Publications and source records attributed to L O'Neill.

At least 19 recordsLinked to original sources
PubMed2001

Relationship between DNA methylation, histone H4 acetylation and gene expression in the mouse imprinted Igf2-H19 domain.

DNA methylation and histone H4 acetylation play a role in gene regulation by modulating the structure of the chromatin. Recently, these two epigenetic modifications have dynamically and physically been linked. Evidence suggests that both modifications are involved in regulating imprinted genes - a subset of genes whose expression depends on their parental origin. Using immunoprecipitation assays, we investigate the relationship between DNA methylation, histone H4 acetylation and gene expression in the well-characterised imprinted Igf2-H19 domain on mouse chromosome 7. A systematic regional analysis of the acetylation status of the domain shows that parental-specific differences in acetylation of the core histone H4 are present in the promoter regions of both Igf2 and H19 genes, with the expressed alleles being more acetylated than the silent alleles. A correlation between DNA methylation, histone hypoacetylation and gene repression is evident only at the promoter region of the H19 gene. Treatment with trichostatin A, a specific inhibitor of histone deacetylase, reduces the expression of the active maternal H19 allele and this can be correlated with regional changes in acetylation within the upstream regulatory domain. The data suggest that histone H4 acetylation and DNA methylation have distinct functions on the maternal and paternal Igf2-H19 domains.

Acetylation↗
PubMed2001

Weekend operating room on call staffing requirements.

This article describes a statistical method used to determine the minimum number of OR teams that should be on call for urgent procedures, in-house versus on standby from home, to minimize labor costs. The OR manager obtains the number of ORs staffed at each hour of the 24-hour period of interest (e.g., 7 AM Saturday to 7 AM Sunday) from the surgical suite's information system. The minimum number of total staffed hours needed to care for patients is calculated for a prespecified level of the acceptable risk of inadequate staffing. A method used to determine whether each staff member should work in-house or on standby from home then is introduced. This method enumerates all possible combinations of shifts to find the one with the lowest cost, and it ensures a prespecified service level. An example based on 248 weeks of data collected from a large surgical suite is presented, and staffing for emergency procedures is reviewed.

Costs and Cost Analysis↗
PubMed2001

An MRP system for surgical linen management at a large hospital.

Materials Requirements Planning (MRP) has been used extensively in manufacturing and other industries to improve on-time delivery and to reduce costs. In this paper, we illustrate how an MRP-type system was developed to monitor surgical linen at a large teaching hospital. We also describe a bar-code scanning 'tag and recapture' study to estimate total inventory. The hospital implemented several changes based upon our recommendations that resulted in time savings and a smoother flow of materials throughout the surgical linen supply chain.

Bedding and Linens↗
PubMed2000

Modulation of innate and acquired immune responses by Escherichia coli heat-labile toxin: distinct pro- and anti-inflammatory effects of the nontoxic AB complex and the enzyme activity.

We have examined the roles of enzyme activity and the nontoxic AB complex of heat-labile toxin (LT) from Escherichia coli on its adjuvant and immunomodulatory properties. LTK63, an LT mutant that is completely devoid of enzyme activity, enhanced Th1 responses to coinjected Ags at low adjuvant dose. In contrast, LTR72, a partially detoxified mutant, enhanced Th2 responses and when administered intranasally to mice before infection with Bordetella pertussis suppressed Th1 responses and delayed bacterial clearance from the lungs. LTR72 or wild-type LT inhibited Ag-induced IFN-gamma production by Th1 cells, and LT enhanced IL-5 production by Th2 cells in vitro. Each of the toxins enhanced B7-1 expression on macrophages, but enhancement of B7-2 expression was dependent on enzyme activity. We also observed distinct effects of the nontoxic AB complex and enzyme activity on inflammatory cytokine production. LT and LTR72 suppressed LPS and IFN-gamma induced TNF-alpha and IL-12 production, but enhanced IL-10 secretion by macrophages in vitro and suppressed IL-12 production in vivo in a murine model of LPS-induced shock. In contrast, LTK63 augmented the production of IL-12 and TNF-alpha. Furthermore, LTK63 enhanced NF-kappaB translocation, whereas low doses of LTR72 or LT failed to activate NF-kappaB, but stimulated cAMP production. Thus, E. coli LT appears to be capable of suppressing Th1 responses and enhancing Th2 responses through the modulatory effects of enzyme activity on NF-kappaB activation and IL-12 production. In contrast, the nontoxic AB complex can stimulate acquired immune responses by activating components of the innate immune system.

Adjuvants, Immunologic↗