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Biomedical subjects

A R Moore

Publications and source records attributed to A R Moore.

At least 37 records · Page 2Linked to original sources
PubMed1996

The cell surface of Aeromonas salmonicida determines in vitro survival in cultured brook trout (Salvelinus fontinalis) peritoneal macrophages.

Aeromonas salmonicida strains phenotypically differing in their A-layer, lipopolysaccharide, and macrophage cytotoxicity were tested in vitro for survivability in brook trout (Salvelinus fontinalis) serum with or without antibodies, and in vivo following intraperitoneal injection. The ability of brook trout peritoneal macrophages to phagocytize and kill the different phenotypes was investigated in an in vitro assay. The virulent strain, A. salmonicida 80204, which has the full complement of known virulence factors, as well as the recently described macrophage cytotoxin, was resistant in vitro to both the bactericidal activity of normal and immune serum, and to brook trout peritoneal macrophages. A. salmonicida SS-70.1, which possesses the A-layer but lacks the cytotoxin, was resistant to the bactericidal activity of normal and immune serum but was avirulent and killed by macrophages. Phenotypes lacking the A-layer, regardless of whether or not they possessed the macrophage cytotoxin were avirulent, susceptible to normal and immune serum and the bactericidal activity of peritoneal macrophages. A. salmonicida virulence expression requires both the A-layer and the macrophage cytotoxin.

Aeromonas↗
PubMed1996

Use of time during body computed tomography scanning in a tertiary care teaching hospital: focus on patient throughput.

RATIONALE AND OBJECTIVES: To control costs, it is increasingly important to make efficient use of imaging technology. We sought to determine and analyze the time required to complete each step of a body computed tomography (CT) scan, focusing on factors that influence patient throughput. METHODS: Over 4 weeks, we prospectively monitored the time required for each step of a body CT scan (i.e., image time, check time, and clear time). Covariate data were collected by patient status: outpatient, inpatient, emergency department (ED), and intensive care unit (ICU); work shift; and radiologist training level (junior resident, senior resident, fellow, and attending). Technologists also predicted whether repeat images would be requested by the radiologist. RESULTS: Three hundred eighty CT examinations were studied: 277 for outpatients, 90 for inpatients, 9 for ED patients, and 4 for ICU patients. The mean total examination time was 44.7 min (mean image time = 33.1 min, mean review time = 8.2 min, and mean clear time = 3.4 min), which did not differ significantly with patient status. A second opinion was sought from a consultant radiologist on the scans of 44 patients. Consultation was requested significantly more frequently (1) by junior residents than by senior residents or fellows and (2) for ED and ICU patients (22% and 50%, respectively) than in outpatients and inpatients (10% and 14%, respectively). Repeat images were obtained from 75 patients, and this was not significantly related to patient status, scan type, or radiologist training level. When the technologist predicted that no repeat images were needed, this prediction agreed with the radiologist in 86% of the cases. When the technologist predicted that repeat images were necessary, this prediction agreed with the radiologist in 56% of the cases. CONCLUSION: Reviewing scans before the patient leaves the CT suite adds considerably to the total time required to complete a scan, particularly if junior residents review scans. If technologists obtain repeat images at their discretion, time would be saved.

Hospitals, Teaching↗
PubMed1996

Heme oxygenase: a novel target for the modulation of the inflammatory response.

Chronic inflammatory diseases place a heavy social and economic burden on the resources of many nations, but the number of safe and effective treatments is limited. To date, the major research effort has concentrated on those mediators responsible for the initiation and maintenance of the pathological process. In contrast, little attention has been focused on endogenous factors responsible for the resolution of the inflammation. Heme oxygenase ((HO); EC 1.14.99.3) is the rate-limiting enzyme in the catabolism of heme to biliverdin (which is converted to bilirubin by biliverdin reductase), free iron and carbon monoxide (CO). Two isoforms of HO have been characterized, the constitutive isoform, HO-2, which is the major isoform present under physiological conditions, and the stress-induced isoform, HO-1, which has also been classified as heat-shock protein 32K (ref. 1). Increases in HO activity have been implicated in tissue protection against oxidative stress. In this communication, we describe the effects of modulating HO during an acute complement-dependent inflammatory response. Elevation of this enzyme resulted in a striking suppression, whereas inhibition of the enzyme led to a potentiation of the inflammatory response. Such novel enzyme modulation has application on the one hand to the treatment of inflammatory diseases and on the other hand to immnosuppressed states in which the impaired ability to mount an adequate inflammatory response may result in death from opportunistic infections.

Animals↗
PubMed1996

Impaired activity of protease inhibitors towards neutrophil elastase bound to human articular cartilage.

OBJECTIVE: To investigate the effects of protease inhibitors on the ability of free and cartilage bound neutrophil elastase to degrade cartilage proteoglycan in vitro. METHODS: Cryostat sections of human articular cartilage were used as substrate, and proteoglycan loss induced by free or cartilage bound elastase was quantified by alcian blue staining, followed by scanning and integrating microdensitometry. RESULTS: High molecular mass protease inhibitors (alpha 1 protease inhibitor, alpha 2 macroglobulin, and soya bean trypsin inhibitor) and synovial fluid from patients with rheumatoid arthritis were effective in blocking proteoglycan loss from sections treated with free elastase, but their activity towards cartilage bound elastase was much reduced. In contrast, low molecular mass elastase inhibitors (N-methoxysuccinyl-Ala-Ala-Pro-Val chloromethyl ketone and ONO-5046 (N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulphonylamino]benzoyl] amino-acetic acid) were effective against free and cartilage bound elastase. CONCLUSION: The binding of elastase to cartilage appears to be a mechanism whereby the enzyme can remain active in the presence of high molecular mass protease inhibitors.

Adult↗
PubMed1995

Polyarthritis in the rat: effects of tolerance and sensitization to the bacterial extract OM-89 with a possible mode of action.

The Bacterial Extract OM-89 has been shown to significantly reduce paw swelling in an avridine-induced polyarthritis (AvPA) in female Wistar rats whether given orally for 3 weeks or as a series of i.p. injections. Paw swelling was also markedly reduced in groups of adult rats which had received i.p. injections of OM-89 as neonates. Three separate tolerance-inducing regimes were used and all were equally effective. It is suggested that OM-89 can modulate the undesirable immunological reactions to endogenous antigens and since oral administration has been shown to be clinically effective in the human, that the induction of oral tolerance could be a mechanism of action of OM-89.

Adjuvants, Immunologic↗
PubMed1995

OM-89 modulation of chronic inflammation: relevance to clinical use.

The modulatory effects of a glycoprotein-rich endotoxin-free extract of Escherichia coli (OM-89) have been studied using the cotton pellet model of chronic inflammation in the male Wistar rat. OM-89 had a suppressive effect on the size of granuloma surrounding implanted cotton pellets at both 4 and 40 mg/kg given three times weekly. The lower dosage of 4 mg was effective throughout and there was little to be gained by increasing the dose as further reduction of granuloma size was not obtained. Whether given prior to, at the same time as, or after an inflammatory stimulus, OM-89 had suppressive effects. However, if given before, animals at first went through a phase of 'sensitization' before suppressive effects were seen on further exposure to OM-89 antigens, a phenomenon which might have bearing on clinical findings in rheumatoid arthritis. In animals presensitized to a cotton pellet, OM-89 was statistically as effective as indomethacin in suppressing a second granuloma. OM-89 combined with indomethacin showed additive effects and was highly effective. The results indicate that OM-89 could be efficacious in the treatment of chronic inflammatory conditions and there is the possibility that in appropriate circumstances OM-89 might replace some drugs currently used and in others reduce their dosage.

Adjuvants, Immunologic↗
PubMed1995

Coronary vasoconstriction in vitro in the hearts of polyarthritic rats: effectiveness of in vivo treatment with the endothelin receptor antagonist SB 209670.

Here we demonstrate that perfused hearts removed from polyarthritic rats develop a pronounced coronary vasoconstriction ex vivo. This vasoconstriction is almost entirely blocked by in vivo pretreatment of the rats with the endothelin receptor antagonist, SB 209670. Thus, inflammatory states may be associated with an increased activity of the endothelin system, leading to vascular dysfunction and vasoconstriction.

Animals↗
PubMed1995

Hyaluronan as a drug delivery system for diclofenac: a hypothesis for mode of action.

Hyaluronan (HA) in combination with diclofenac is currently undergoing clinical trials as a topical preparation in the management of osteoarthritic pain, basal-cell carcinoma and actinic keratosis. These are clearly diverse pathologies, but in all cases substance P plays a central role either directly or through secondary mediators such as prostaglandin E2 and nitric oxide. A common mechanism for HA in combination with diclofenac in these conditions may be through ameliorating the direct and indirect effects of substance P. Additionally, HA appears to depot and hold diclofenac in the epidermis, thereby prolonging its pharmacokinetic half-life. In rabbits, stenosis following balloon angioplasty is prevented by a subcutaneous dose of HA, probably through blockade of cell-surface HA receptors (ICAM-1, CD44 & RHAMM). The physicochemical properties of HA, and the binding of HA to HA receptors, suggests that HA will have value as a novel drug delivery system.

Animals↗
PubMed1995

Is tolerance induction a possible mode of action of OM-89?

Neonatal Wistar rats were injected intraperitoneally with either 20 mu g OM-89 at birth and on day 3 after birth or 2 mg three times weekly until 200 g body weight. At this weight, groups were either implanted subcutaneously with a cotton pellet to induce granuloma, or had avridine polyarthritis or pleurisy induced. Both OM-89 treatment regimes significantly reduced granuloma weight (p < 0.05 and < 0.01), paw volume (p < 0.001) and pleural exudates (p < 0.01). The results suggest that OM-89 could work via tolerance induction.

Adjuvants, Immunologic↗
PubMed1994

Cyclo-oxygenase and nitric oxide synthase isoforms in rat carrageenin-induced pleurisy.

1. The profiles of cyclo-oxygenase (COX) and nitric oxide synthase (NOS) isoforms were determined in the rat carrageenin-induced pleurisy model of acute inflammation. 2. The enzymes were assessed in peripheral blood leucocyte (PBL) cell pellets taken from untreated animals and at 2, 6 and 24 h after injection of the irritant in pleural exudate cell pellets and lung homogenates. 3. COX activity was assessed by the generation of prostacyclin (PGI2, measured as the stable metabolite, 6-keto prostaglandin F1 alpha) and prostaglandin E2 (PGE2). Western blot analysis and immunohistochemistry were also carried out. 4. NOS activity was based on the conversion of [3H]-L-arginine to [3H]-L-citrulline in the presence (total NOS activity) or absence of Ca2+ (inducible NOS; iNOS). 5. Peripheral blood leucocyte samples contained low levels of COX activity. In pleural exudate cell pellets, COX activity peaked at 2 to 6 h after injection of the carrageenin. At 24 h, COX activity was significantly reduced. 6. Western blot analysis demonstrated that the inducible isoform of COX (COX-2), was the predominant enzyme at all time points. Low levels of COX-2 were seen in PBLs. In pleural exudate cell pellets maximal COX-2 protein levels were seen at 2 h. 7. Immunohistochemistry confirmed the findings of Western blot studies. Approximately 10% of polymorphonuclear neutrophils (PMNs) in PBLs from untreated animals were immunopositive for COX-2. In cell pellet smears from carrageenin-induced pleurisy taken 2 h after injection of the irritant, PMNs were also the major source of COX-2 immunoreactivity. A small proportion of macrophages and mesothelial cells were also immunolabelled for COX-2.8. Low levels of NOS activity were seen in PBLs. In pleural exudates NOS activity was maximum at 6 h and greatly reduced by 24 h. This activity was solely attributable to iNOS.9. The present results illustrated a similar profile of COX and NOS activity in the carrageenin-induced pleurisy model of acute inflammation. It was demonstrated that COX-2 and iNOS were the predominant isoforms of their respective enzymes.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Direct degradation of articular cartilage by rheumatoid synovial fluid: contribution of proteolytic enzymes.

OBJECTIVE: To test the effects of synovial fluids (SF) on human cartilage in an in vitro model. METHODS: Freshly collected SF were incubated with cryostat sections of articular cartilage, and glycosaminoglycan (GAG) loss determined by microdensitometry after alcian blue staining. RESULTS: Of 20 rheumatoid SF, 11 induced significant GAG loss compared with only 3 out of 15 osteoarthritic SF. The effect of rheumatoid fluids appeared to be related to disease activity. GAG loss was partially prevented by a broad spectrum serine protease inhibitor and a specific elastase inhibitor. Cartilage degrading activity was lost on storage which may explain why it has not been widely reported before. CONCLUSION: Rheumatoid SF can directly degrade cartilage through the action of proteases. There is an involvement of serine proteases, elastase in particular.

Adult↗
PubMed1993

Interaction between neutrophil-derived elastase and reactive oxygen species in cartilage degradation.

The role of proteases and reactive oxygen species (ROS) in polymorphonuclear neutrophil (PMN) induced cartilage degradation in vitro were studied. ONO-5046, a novel synthetic elastase inhibitor, significantly and dose dependently protected cartilage from degradation induced by PMNs stimulated with phorbol myristate acetate (PMA), opsonized zymosan, N-formyl-methionyl-leucyl-phenylalanine plus cytochalasin-B, or A-23187. The degradation by PMA-stimulated PMNs was unaffected by protease inhibitors which lack anti-elastase activity. However, the hydrogen peroxide (H2O2) reducing agent catalase afforded significant protection. Measurement of elastase activity following PMN activation by PMA showed that antioxidants which reduce H2O2 and/or hypochlorous acid decreased elastase activity. Thus, it is suggested that an indirect interaction between ROS and elastase activity may exist in PMN induced cartilage degradation. Furthermore, the possible implication of an endogenous elastase inhibitor(s) is discussed.

Animals↗
PubMed1993

Cartilage degradation by polymorphonuclear leucocytes: in vitro assessment of the pathogenic mechanisms.

Polymorphonuclear leucocytes (PMNs), which predominate in inflammatory synovial fluid, can degrade cartilage. This was measured by a novel in vitro model; PMNs were incubated for up to one hour with 2 or 3 microns sections of cartilage and the glycosaminoglycan loss determined by microdensitometry after alcian blue staining. Glycosaminoglycan loss could be as a result of damage from reactive oxygen species, proteolytic enzymes, or a combination of the two. The relative contributions of these mechanisms were evaluated using selective inhibitors. The results show that activated PMNs will degrade cartilage and that this degradation is due to proteolytic enzymes and not reactive oxygen species. There is a specificity involving elastase but not other serine proteases. It is suggested that enzyme inhibition may play a part in reducing PMN mediated cartilage damage.

Animals↗
PubMed1993

Comparison of surface fibroblastic cells in subcutaneous air pouch and synovial lining: differences in uridine diphosphoglucose dehydrogenase activity.

In contrast to synovial tissue, rat subcutaneous air pouch lining was found to lack cells showing high activity of uridine diphosphoglucose dehydrogenase, an enzyme involved in hyaluronan synthesis. This indicates that the properties of cells on the surface of synovium are not determined simply by tissue cavitation. Shearing forces may be more important in inducing the specialized behaviour of synovial surface fibroblasts.

Air↗
PubMed1991

A novel in vitro method for investigating cartilage degradation.

A novel in vitro microassay is described which allows the direct effects of short-lived cells or transient cell processes on cartilage matrix to be investigated. The method involves layering cells onto 2 microns cryostat sections of cartilage and assessing matrix integrity with quantitative histochemistry. Rat polymorphonuclear neutrophils (PMNs) caused glycosaminoglycan (GAG) loss from sections of bovine nasal cartilage. This loss of GAG was greatly enhanced by the presence of zymosan, phorbol ester or calcium ionophore. Similar results were obtained using human articular cartilage with human PMNs. This technique may be useful in the detection of novel chondroprotective agents.

Animals↗