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S O'Neill

Publications and source records attributed to S O'Neill.

At least 91 records · Page 5Linked to original sources
PubMed1991

S-nitrosocysteine inhibition of human platelet secretion is correlated with increases in platelet cGMP levels.

Platelet inhibition by exogenous and endogenous nitrovasodilators has been shown to be associated with increases in cGMP, but proof of a role for cGMP in this process is lacking. We therefore studied the effects of cGMP and guanylate cyclase stimulation on human platelet secretion by pharmacologically modulating intraplatelet cGMP levels. The endothelium-derived relaxing factor (EDRF)-like activator of guanylate cyclase, S-nitrosocysteine (SNOC), led to a dose-dependent inhibition of secretion in intact human platelets (IC50 = 10(-6) M). The cGMP phosphodiesterase inhibitor M&B 22,948 augmented SNOC-induced inhibition of secretion through elevations in cGMP without affecting cAMP levels (from 50% to 81% inhibition versus control, p = 0.02). Methylene blue reversed the inhibitory effects of SNOC on platelet secretion (p = 0.03). Dibutyryl-cGMP and 8-bromo-cGMP also significantly inhibited secretion in this system. Incubation of platelets with exogenous cGMP to achieve intraplatelet cGMP levels comparable to those after SNOC treatment resulted in similar degrees of inhibition of secretion (32% inhibition versus control, p = 0.01) and was also potentiated by M&B 22,948 (from 32% to 68% inhibition, p = 0.003). In addition, a highly significant correlation between intraplatelet cGMP levels and the degree of inhibition of secretion was demonstrable in these studies (r = 0.94, p = 0.016). These data demonstrate that elevation of intraplatelet cGMP levels by the EDRF-like compound SNOC is correlated with inhibition of human platelet secretion.

Blood Platelets↗
PubMed1990

Inhibition of fibrinogen binding to human platelets by S-nitroso-N-acetylcysteine.

Because of the central role of fibrinogen binding in platelet aggregation and recent evidence implicating S-nitrosothiol compounds in the platelet inhibitory effects of endogenous and exogenous organic nitrate compounds, we examined the effect of the S-nitrosothiol S-nitroso-N-acetylcysteine (SNOAC) on fibrinogen binding to gel-filtered human platelets. We found that SNOAC markedly inhibited the binding of fibrinogen to normal human platelets in a dose-dependent fashion and that this inhibitory effect was the result of both an increase in the apparent Kd of the platelet receptor for the fibrinogen molecule (from 6.8 x 10(-7) to 1.8 x 10(-6) M, a 2.7-fold increase) and a decrease in the total number of fibrinogen molecules bound to the platelet (from 76,200 to 38,250, a 50% decrease). In addition, we noted a rapid, dose-dependent rise in platelet cyclic GMP levels following exposure of platelets to SNOAC which was significantly inversely correlated with fibrinogen binding and was accompanied by inhibition of intracellular calcium flux in response to a variety of platelet agonists. Similar dose-dependent inhibition of fibrinogen binding was found in the presence of cyclic GMP analogues and was significantly enhanced by inhibition of platelet cyclic GMP phosphodiesterase. These results describe the inhibition of platelet fibrinogen binding by an S-nitrosothiol compound, help define the biochemical mechanism by which S-nitrosothiols inhibit platelet aggregation, and lend support to the view that cyclic GMP is an important inhibitory intracellular mediator in human platelets.

Acetylcysteine↗
PubMed1989

Recurrent vulvovaginal candidiasis. A gynaecological enigma.

This article draws attention to a common condition that causes women, their partners and, to a lesser extent, their doctors considerable distress. A review of the recent literature gives an idea of the present scientific thinking on the pathogenesis and management of recurrent vulvovaginal candidiasis.

Candidiasis, Vulvovaginal↗
PubMed1989

Hypophosphatemia complicating bronchodilator therapy for acute severe asthma.

Hypophosphatemia has been recently highlighted as a reversible cause of respiratory muscle hypocontractility and reduced tissue oxygen extraction in patients with chronic obstructive lung disease and asthma. To define the prevalence and mechanism of hypophosphatemia under these circumstances, we studied phosphate homeostasis in 22 patients with chronic asthma, who had been hospitalized for emergency bronchodilator therapy. Serum phosphate concentration was normal in all patients on presentation, and fell after the initiation of bronchodilator therapy. Twelve patients (54%) developed hypophosphatemia (serum phosphate, less than 0.8 mmol/L). Urinary phosphate level fell in parallel. A negative correlation was observed between serum phosphate and serum theophylline concentrations, and a positive correlation between serum and urinary phosphate concentrations. No correlation was found between serum phosphate and serum albumin or urea concentration. These data indicate that hypophosphatemia is a common metabolic abnormality during the emergency treatment of asthma. The underlying mechanism appears to be drug-induced phosphate flux from the extra-cellular to the intracellular space. We suggest that the serum phosphate level be monitored in patients undergoing emergency treatment of bronchospasm, particularly if a prolonged period of bronchodilator therapy is required or if respiratory muscle fatigue supervenes.

Adolescent↗
PubMed1986

An enzyme immunoassay to measure canine circulating fibronectin.

A competitive enzyme immunoassay has been used to detect and quantitate fibronectin in canine plasma. In this test, purified fibronectin, bound to microtiter plates, competes with plasma fibronectin for the conjugated antibody, rabbit-anticanine, fibronectin-horseradish peroxidase. The assay could detect fibronectin in purified standards from 58 ng/ml to 580 microgram/ml. The range of 1-100 microgram/ml was linear for plasma samples diluted 1:10, allowing samples with fibronectin concentrations from 10-1000 microgram/ml to be easily measured by this method. The mean normal fibronectin concentration of 132 dogs, by this method, was determined to be 320 +/- 74 microgram/ml.

Journal Article↗
PubMed1985

Activation of rat and human alveolar macrophage intracellular microbicidal activity by a preformed LGL cytokine.

An alveolar macrophage-activating factor was released from Percoll fractionated large granular lymphocytes (LGL) within minutes of contact with either the natural killer (NK)-sensitive K562 tumor or heat-killed Staphylococcus aureus. The factor enhanced the intracellular killing of S. aureus without altering the rate of phagocytosis. Factor release was blocked by treatment of LGL with monensin, a carboxylic ionophore that inhibits vesicular traffic, but was unaffected by actinomycin D and cycloheximide pretreatment, suggesting that the cytokine was performed. The cell producing the factor was found only in Percoll fractions containing high concentrations of lytic NK cells and LGL, and the phenotypes of the LGL were HNK-1+ and E rosette-. The macrophage activating factor was a small protein of 10,000 to 20,000 daltons, as determined by gel fractionation, and was sensitive to proteolytic enzymes and heat and pH labile. Active supernatants were devoid of antiviral (interferon; IFN) or interleukin 2 (IL 2) activity, and IFN-beta, IFN-gamma, IL 2, and interleukin 1 were unable to activate staphylococcidal activity, suggesting that the LGL macrophage activating factor was distinguishable from these cytokines.

Animals↗
PubMed1985

Plasma fibronectin concentrations in dogs with disseminated intravascular coagulation.

Plasma fibronectin concentrations were significantly (P less than 0.001) below the reference range in dogs with disseminated intravascular coagulation (DIC) secondary to nonlymphomatous neoplasia, acute necrotizing pancreatitis, sepsis, chronic active hepatitis, and heat stroke. There was no statistical evidence of a group effect. Decrease in fibronectin concentration was associated with severe DIC, although no attempt was made to correlate fibronectin concentration with prognosis. These findings parallel those reported for severely ill human beings with diseases associated with DIC. They exemplify the potential of spontaneous diseases in animals as models for the study of human disease.

Acute Disease↗
PubMed1984

Rat lung lavage surfactant enhances bacterial phagocytosis and intracellular killing by alveolar macrophages.

We have tested the effect of a preparation of rat lung lavage surfactant (SAM) on phagocytosis and intracellular killing of Staphylococcus aureus by rat alveolar macrophages (AMs). The SAM was isolated and purified by density gradient centrifugation. It was highly enriched in disaturated phosphatidylcholine, and invariably lowered the surface tension of a clean saline solution to less than 10 dynes/cm at 37 degrees C. We used a radiometric assay to measure phagocytosis as uptake by AMs of 14C phenylalanine labelled staphylococci, and intracellular killing as incorporation of 3H thymidine by viable staphylococci from the lysed AMs. When staphylococci were incubated with 100 to 300 micrograms of SAM, both phagocytosis and intracellular killing efficiency were enhanced. The mean numbers of intracellular staphylococci/AM were 24.3 +/- 3.8 and 18.3 +/- 3.0 in the SAM and control groups, respectively (p less than 0.001). The mean intracellular killing efficiency was 59.6 +/- 6.76% and 39.7 +/- 7.17% in the SAM and control groups, respectively (p less than 0.001). Previous studies have shown that unpurified rat lung lavage fluid enhances intracellular killing of staphylococci by AMs. Our results suggest that SAM may be the active principle in lung lavage fluid that enhances intracellular killing. In addition, in our test system, SAM enhanced staphylococcal phagocytosis by AMs.

Animals↗
PubMed1984

Survival after high blood alcohol levels. Association with first-order elimination kinetics.

A patient survived acute alcohol intoxication with an unprecedented blood alcohol level of 1,500 mg/dL. Treatment included peritoneal dialysis and intravenously administered fructose. Alcohol elimination followed first-order kinetics, in which the elimination rate is proportional to concentration, rather than zero order in which the metabolic rate is independent of concentration. The report provides further evidence for first-order elimination kinetics with high blood alcohol levels and for an adaptive increase in alcohol metabolism with long-term alcohol consumption.

Adult↗