PubMed Health⌕ Search

Biomedical subjects

B G Oliver

Publications and source records attributed to B G Oliver.

9 recordsLinked to original sources
PubMed2003

Regulation of protease-activated receptor-1 in mononuclear cells by neutrophil proteases.

Neutrophils and mononuclear cells are implicated in the pathogenesis of several inflammatory conditions including chronic obstructive pulmonary disease (COPD). Neutrophil-derived serine proteases, such as cathepsin G (CG) and neutrophil elastase (NE), may interact with mononuclear cells via protease-activated receptors (PARs) which are seven-transmembrane G protein-coupled receptors activated by proteolytic cleavage of the extracellular N-terminus, and which, on activation, induce the release of several mediators and cytokines. We determined whether CG and NE could affect PAR-1 expression and function in mononuclear cells. Human blood mononuclear cells were isolated from 20 healthy donors. Surface and intracellular receptor expression and calcium mobilisation (using the calcium chelator, FLUO3-AM) were studied by fluorescence-assisted cell sorting (FACS analysis). Positive controls, i.e. thrombin (0.1-100 mU/ml) and the PAR-1-activating peptide SFLLRN (100 microM) induced a rapid and transient intemalisation of PAR-1 in monocytes and lymphocytes. CG but not NE had a similar effect. By contrast, in monocytes intracellular calcium mobilisation was induced by thrombin and SFLLRN but not by CG and NE. Thus, CG can induce intracellular PAR-1 sequestration without activation of the receptor, and may act as an antagonist and prevent subsequent activation of PAR-1 in mononuclear cells. These findings may be of relevance to the pathogenesis of COPD.

Calcium↗
PubMed2001

Identification of genes of Aspergillus fumigatus up-regulated during growth on endothelial cells.

Aspergillus fumigatus is an important opportunistic fungal pathogen that can cause acute invasive disease in neutropenic hosts. Invasive aspergillosis is being diagnosed with increasing frequency, and morbidity and mortality remain high despite prompt antifungal therapy. Because little is known about the virulence factors used by A. fumigatus, a tissue culture model was developed to mimic the interaction of the fungus with the endothelium. Differential display was used to compare gene expression in fungal cells grown on endothelial cells with that of cells grown in the absence of endothelial cell contact, and genes that were up-regulated were selected for analysis as putatively virulence-related genes. Two of these up-regulated genes were chosen for further study and were identified as genes encoding the regulatory subunit of cyclic adenosine monophosphate (cAMP)-dependent protein kinase and a member of the ras gene family, both of which are involved in cAMP-mediated signaling in fungi. This model system provides a new approach to the identification of potentially virulence-related genes induced in A. fumigatus by the interaction with host cells.

Amino Acid Sequence↗
PubMed2000

Balance of matrix metalloprotease-9 and tissue inhibitor of metalloprotease-1 from alveolar macrophages in cigarette smokers. Regulation by interleukin-10.

An imbalance between proteases and antiproteases may play a role in emphysema, which is characterized by increased degradation of extracellular matrix, and in airway remodeling in chronic bronchitis and asthma, in which there is increased collagen deposition. We assessed the effect of smoking on release of matrix metalloprotease-9 (MMP-9) and of its inhibitor, tissue inhibitor of metalloprotease-1 (TIMP-1), from alveolar macrophages, and determined the effects of proinflammatory (interleukin [IL]-1beta and lipopolysaccharide [LPS]) and antiinflammatory (IL-10) stimuli on the release of MMP-9 and TIMP-1. We performed bronchoalveolar lavage in 11 smokers and 11 nonsmokers, and cultured airway macrophages in the presence of control medium, IL-1beta, and LPS. Airway macrophages from smokers released greater amounts of MMP-9 and TIMP-1 at baseline and in response to IL-1beta and LPS than did those of nonsmokers. Airway macrophages from smokers produced more TNF-alpha and IL-10. IL-10 increased TIMP-1 release without modifying that of MMP-9, leading to a decrease in the MMP-9 to TIMP-1 ratio. Anti-IL-10 antibody had no effect on MMP-9 production induced by LPS. We conclude that the release of proteases and antiproteases by airway macrophages is increased in cigarette smokers, and can be regulated by exogenous IL-10.

Adult↗
PubMed1996

Novel role for Sp1 in phorbol ester enhancement of human platelet thromboxane receptor gene expression.

Expression of platelet thromboxane receptors is transcriptionally increased during megakaryocytic differentiation stimulated by phorbol 12-myristate 13-acetate (PMA). We previously cloned and characterized the promoter region of the human thromboxane receptor gene and localized PMA-responsive elements to a region between 1.84 and 1.95 kilobase pairs (kb) 5' of the transcription initiation site (D'Angelo, D. D., Davis, M. G., Houser, W. A., Eubank, J. J., Ritchie, M. E., and Dorn, G. W., II (1995) Circ. Res. 77, 466-474). Herein we report the localization of the PMA response element to a 14-nucleotide C-rich sequence, flanked by an octanucleotide inverted repeat, located -1.938 to -1.925 kb 5' of the transcription start site of this gene. We further identify the PMA-responsive enhancer factor that binds to this C-rich sequence as Sp1. Heterologous thromboxane receptor gene promoter/thymidilate kinase reporter constructs transfected into K562 cells exhibited PMA responsiveness when the C-rich element was included with additional 3' sequence from -1.924 to -1.84 kb. However, mutations of the C-rich element that disrupted a GC box located on the inverse strand eliminated PMA responsiveness and, in gel mobility shift assays, eliminated binding of Sp1. PMA treatment of K562 cells significantly increased, by 5-fold, Sp1 binding to the C-rich element and increased both phosphorylated and nonphosphorylated Sp1 protein levels by 2-fold. Furthermore, PMA treatment transiently increased Sp1 mRNA levels prior to increasing thromboxane receptor mRNA, suggesting that up-regulation of Sp1 contributes to up-regulation of thromboxane receptors. Finally, we have detected an unidentified K562 nuclear protein that binds specifically to the sense strand of the C-rich sequence overlapping the Sp1 binding site and that, by stabilizing a double stem-loop conformation of this DNA segment, may also play a role in Sp1 regulation of this gene. These studies are the first to describe regulatory and regulated roles for Sp1 in PMA-responsive gene expression and suggest that modulation of Sp1 levels controls thromboxane receptor expression during megakaryocytic differentiation.

Base Composition↗
PubMed1988

Urinary tract infections in the surgical patient.

Urinary tract infection (UTI) continues to be a common nosocomial infection. From a 2-year city-county hospital experience, 212 nosocomial UTI were identified in 153 patients from 3747 admissions. Mean age was 54 years; 102 were men. Foley catheterization was an associated factor in 129 patients (84%). UTI was caused by 40 different species of bacteria. In 28 infections (13%), the UTI was polymicrobial. Only nine patients had bacteremia. The bacteriology of the UTI depended on whether the patient had received systemic antibiotics previously during the hospitalization. Prior antibiotic administration increased the probability of Pseudomonas and Serratia as pathogens. Thus, patients that have had antibiotic therapy demonstrate a distribution of pathogens that are different from patients not receiving antibiotics, and a distribution different from the community-acquired UTI. Continued emphasis on the shorter duration and more judicious use of systemic antibiotics for both prophylaxis and therapy is warranted.

Adolescent↗
PubMed1982

Extraction and clean-up procedures for measuring chlorobenzenes in sediments and fish by capillary gas chromatography.

A soxhlet extraction technique for recovering chlorobenzenes from sediments and fish is described. The extract is concentrated by evaporation, cleaned up with florisil (sediments) or a combination of alumina, silica gel, florisil and acidified silica gel (fish) before quantitation by capillary gas chromatography with an electron capture detector. Recoveries for all chlorobenzenes are greater than 80%. Detection limits of the technique are approximately 0.05 ng/g (ppb) for penta- and hexachlorobenzene, approximately 0.2 ppb for the tetrachlorobenzenes, approximately 0.4 ppb for the trichlorobenzenes, approximately 5 ppb for the dichlorobenzenes, and approximately 1500 ppb for monochlorobenzene.

Animals↗
PubMed1975

Metal concentrations in the sewage, effluents, and sludges of some southern Ontario wastewater treatment plants.

Aluminum, barium, berylliu, bismuth, cadmium, chromium, cobalt, copper, iron, lead, manganese, mercury, molybdenum, nickel, silver, strontium, vanadium and zinc concentrations in the sewage, effluents and sludges of ten southern Ontario wastewater treatment plants are reported. The efficiency for metal removal by a conventional activated sludge plant was determined. The effect of metal concentrations in receiving waters from residual metals in sewage effluents is discussed. The environmental hazards of disposing of sewage sludges with high metal content on agricultural land is considered.

Aluminum↗