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R Wilson

Publications and source records attributed to R Wilson.

At least 37 records · Page 2Linked to original sources
PubMed1992

Monte Carlo simulation of rodent carcinogenicity bioassays.

In this paper we describe a simulation, by Monte Carlo methods, of the results of rodent carcinogenicity bioassays. Our aim is to study how the observed correlation between carcinogenic potency (beta or 1n2/TD50) and maximum tolerated dose (MTD) arises, and whether the existence of this correlation leads to an artificial correlation between carcinogenic potencies in rats and mice. The validity of the bioassay results depends upon, among other things, certain biases in the experimental design of the bioassays. These include selection of chemicals for bioassay and details of the experimental protocol, including dose levels. We use as variables in our simulation the following factors: (1) dose group size, (2) number of dose groups, (3) tumor rate in the control (zero-dose) group, (4) distribution of the MTD values of the group of chemicals as specified by the mean and standard deviation, (5) the degree of correlation between beta and the MTD, as given by the standard deviation of the random error term in the linear regression of log beta on log (1/MTD), and (6) an upper limit on the number of animals with tumors. Monte Carlo simulation can show whether the information present in the existing rodent bioassay database is sufficient to reject the validity of the proposed interspecies correlations at a given level of stringency. We hope that such analysis will be useful for future bioassay design, and more importantly, for discussion of the whole NCI/NTP program.

Animals↗
PubMed1992

Clindamycin, erythromycin, and roxithromycin inhibit the proinflammatory interactions of Pseudomonas aeruginosa pigments with human neutrophils in vitro.

The Pseudomonas aeruginosa-derived phenazine pigments pyocyanin and 1-hydroxyphenazine (1-hp) prime human neutrophils for enhanced, stimulus-activated release of superoxide and myeloperoxidase (MPO), respectively. In the present study, the modulatory potentials of the antimicrobial agents clindamycin, erythromycin, and roxithromycin (10 and 20 micrograms/ml) on the prooxidative interactions of pyocyanin and 1-hp (12.5 microM) with human neutrophils have been investigated. Clindamycin, erythromycin, and especially roxithromycin caused dose-related inhibition of the generation of superoxide by both untreated and pyocyanin-treated neutrophils during activation with either the synthetic chemotactic tripeptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) or the calcium ionophore A23187. The antimicrobial agents also inhibited the generation of reactive oxidants by the MPO-H2O2-halide system during activation of both untreated and 1-hp-treated neutrophils by FMLP. These effects appeared to be due to drug-related interference with membrane-associated oxidative metabolism, since none of the antimicrobial agents inhibited the release of MPO by activated neutrophils, nor did they possess oxidant-scavenging properties. These data demonstrate that clindamycin, erythromycin, and especially roxithromycin antagonize the proinflammatory interactions of pyocyanin and 1-hp with neutrophils and indicate a possible therapeutic role for these antimicrobial agents in the prevention of tissue damage in diseases characterized by P. aeruginosa infection.

Clindamycin↗
PubMed1992

Effect of immunization with Freund's adjuvant and pneumolysin on histologic features of pneumococcal infection in the rat lung in vivo.

Immunization with Freund's adjuvant and pneumolysin and stimulation with Freund's adjuvant alone both reduced the severity of the pneumonia caused by injections of bacteria into the apical lobe bronchi of rats. Neither protocol influenced the incidence of pneumococcal bacteremia. Illness sufficiently severe to require sacrifice was delayed from 2.8 days in nonimmunized animals to 5.7 days in those immunized with Freund's adjuvant and pneumolysin (P < 0.05) and 4.5 days in those stimulated with Freund's adjuvant alone (P, not significant).

Adjuvants, Immunologic↗
PubMed1992

Interaction of capsulate Haemophilus influenzae with human airway mucosa in vitro.

Two pairs of isogenic capsulate and noncapsulate and one pair of capsulate fimbriate and nonfimbriate strains of Haemophilus influenzae type b were studied in an organ culture of human respiratory mucosa. Over 24 h, the numbers of recovered bacteria increased from the original inoculum size of 10(5) to 10(8) CFU/ml. Transmission electron microscopy and scanning electron microscopy showed that noncapsulate organisms caused significant epithelial damage, whereas capsulate strains did not. Association of noncapsulate bacteria with damaged epithelial cells was observed by 14 h of incubation. In contrast, capsulate organisms were associated with a dense, thick, gel-like matrix which was observed above the epithelial surface. These capsulate organisms were not seen to associate with the epithelial surface (by transmission electron microscopy), though they were occasionally seen adhering to cells by scanning electron microscopy. Fimbriate capsulate H. influenzae showed increased adherence to buccal cells compared with nonfimbriate capsulate organisms. There was also association of fimbriate capsulate bacteria with damaged organ culture epithelium in one of four experiments. It is concluded that both capsule and fimbriae affect the interaction of H. influenzae with human airway mucosa in vitro by influencing adherence to and damage of the epithelium.

Bacterial Adhesion↗
PubMed1992

Release of mucus glycoconjugates by Pseudomonas aeruginosa rhamnolipid into feline trachea in vivo and human bronchus in vitro.

Pseudomonas aeruginosa colonizes the lower respiratory tracts of patients with severe bronchiectasis, including cystic fibrosis, a condition associated with increased airway mucus output. We have shown that an extract containing chloroform-soluble extracellular products of P. aeruginosa releases glycoconjugates into the cat trachea in vivo. This activity was not related to pyocyanin, a major component of the extract, but was associated with the rhamnolipids. Purified monorhamnolipid (100 micrograms/ml) released radiolabeled and periodic acid-Schiff (PAS)-reactive glycoconjugates (delta 3H = +490 +/- 70%, delta 35S = +170 +/- 40%, delta PAS = +8.6 +/- 1.7 micrograms/min; n = 6, P less than 0.02 for each). Dirhamnolipid (200 micrograms/ml) was also effective (delta 3H = +640 +/- 70%, delta 35S = +130 +/- 20%, delta PAS = +9.3 +/- 1.5 micrograms/min; n = 6, P less than 0.02 for each). Monorhamnolipid (100 micrograms/ml) also released 35S-labeled and PAS-reactive glycoconjugates from human bronchial tissue in vitro (delta 35S = +189 +/- 47%, delta PAS = +26.3 +/- 8.5 micrograms/min; n = 7, P less than 0.001 versus control tissues in which no stimulus was given). The cat tracheal glycoconjugates released by the rhamnolipids differed from those released by pilocarpine 50 microM, in having a higher 3H:35S ratio (P less than 0.001). After gel chromatography on a Sepharose CL-4B column, the void volume fractions of the glycoconjugates also had different profiles in a cesium chloride density gradient. Those released by rhamnolipid banded at 1.62 g/ml, while those released by pilocarpine banded mainly at 1.50 g/ml, with some of the higher density material also present.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Anti-ganglioside antibodies in peripheral neuropathy.

There have recently been reports that patients with motor neuropathy with multifocal conduction block have high circulating levels of antibodies to the ganglioside GM1. Other reports have described the presence of these antibodies in patients with inflammatory demyelinating neuropathy and patients with lower motor neurone forms of motor neurone disease. We have established an ELISA assay for IgG and IgM antibodies to asialo-GM1 (Sigma). We used this assay to measure such antibodies in serum from normal subjects and from patients with various neurological conditions. In normal subjects, antibodies to asialo-GM1 were present only in low levels. An arbitrary scale with an upper limit of normal was established. Initial studies have found that abnormally high levels of IgG antibodies to asialo-GM1 were present in 4 of 9 patients with inflammatory demyelinating neuropathies (Guillain-Barré syndrome or chronic inflammatory demyelinating polyradiculoneuropathy). We found one patient with a monoclonal IgM circulating paraprotein and a motor neuropathy who had a high titre of antibody to asialo-GM1. As yet we have found no patients with motor neurone disease with antibodies to asialo-GM1.

Antibodies↗
PubMed1992

Reverse redistribution on exercise thallium scintigraphy: relationship to coronary patency and ventricular function after myocardial infarction.

OBJECTIVE: To define prevalence, pathophysiology and relation to thrombolytic therapy of reverse redistribution (appearance of a new, or worsening of an existing, scintigraphic defect on 4 h delayed images compared with the stress thallium image). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Referral centre. PATIENTS: Sixty-three patients with acute myocardial infarction. INTERVENTIONS: Tomographic exercise thallium scintigraphy, radionuclide angiography, and quantitative coronary angiography. MAIN RESULTS: Tomographic exercise thallium scintigraphy performed at day 10 revealed fixed defects in 15 patients, reversible defects in 22 patients and reverse redistribution in 26 patients; no difference in treatment assignment (tissue plasminogen activator versus placebo) was found among the three groups. Left ventricular function was similar in patients with fixed or reversible defects and reverse redistribution; global ejection fraction was 48 +/- 14, 51 +/- 10 and 48 +/- 5%, respectively, and regional infarct ejection fraction was 36 +/- 15, 40 +/- 13 and 37 +/- 18%, respectively. However, nitroglycerin administration resulted in a significantly greater improvement in regional ejection fraction in reverse redistribution patients (5 +/- 4%) than that in patients with fixed defect (2 +/- 5%, P < 0.05) or reversible defects (3 +/- 5%, P < 0.05). The infarct-related artery had a greater cross-sectional area in reverse redistribution patients (1.5 +/- 1.42 mm2) compared with those with reversible defects (0.50 +/- 0.26 mm2, P < 0.05), but was similar to fixed defect patients (1.04 +/- 0.88). CONCLUSIONS: Reverse redistribution on tomographic thallium scintigraphy is a frequent phenomenon (occurring in 40% of patients following acute myocardial infarction) and is independent of thrombolytic therapy. Patients with reverse redistribution have a more widely patent infarct-related artery and similar ventricular function, but significantly greater functional improvement following nitroglycerin administration compared with those with reversible or fixed defects. These data suggest myocardial salvage within the infarct zone in some patients with reverse redistribution.

Animals↗
PubMed1991

Effects of long-term vasodilator therapy on electrocardiographic abnormalities in chronic aortic regurgitation.

Electrocardiographic abnormalities develop in patients with chronic aortic regurgitation (AR). Although vasodilator drugs may reduce left ventricular (LV) volume overload, the effects of such therapy on electrocardiographic abnormalities have not been previously evaluated. Accordingly, electrocardiograms were analyzed before and after double-blind, randomized administration of either hydralazine or placebo in 54 patients with chronic AR. These patients were without limiting symptoms and had preserved ejection fraction on entry in the study. The magnitude of ST-segment depression and Romhilt-Estes point score for LV hypertrophy were assessed. Baseline ST depression and LV hypertrophy scores in the placebo and hydralazine groups were not significantly different. At follow-up, after a mean of 19 +/- 6 months, there was a significant reduction in ST depression in patients taking hydralazine (n = 28) compared with patients given placebo (n = 26): -0.023 +/- 0.044 vs 0.029 +/- 0.055 mV, respectively (p = 0.0001); and in the LV hypertrophy score (-1.1 +/- 2.2 vs 0.9 +/- 2.3 points, respectively; p = 0.002). Hydralazine-treated patients also had significant decreases in LV end-diastolic and end-systolic volume indexes, and a significant increase in ejection fraction. These results suggest that such vasodilator therapy may be beneficial in patients with chronic AR.

Adult↗
PubMed1991

Clinical analysis in intact erythrocytes using 1H spin echo NMR.

A new method of clinical analysis based on 1H spin echo NMR spectroscopy is presented. It is capable of providing information on six metabolites within viable erythrocytes, directly and without any preparative procedures prior to analysis except for cell separation and washing. Erythrocytes from patients with rheumatoid arthritis and Graves' disease are compared with cells obtained from healthy volunteers. The NMR detectable species in the cytosol of the cells are glutathione, ergothioneine, choline, creatine, glycine, lactate and to a lesser extent alanine and valine. Significant differences are observed between the ergothioneine pools in the rheumatoid group (P less than 0.01) compared to the control group. The glutathione: di-glutathione ratio can be assessed from the ratio, g2 to g4, taken from different signals in the glutathione molecule. The total concentration of glutathione present is easily assessed qualitatively but is more difficult to quantitate.

Adult↗
PubMed1991

Recurrent abortion.

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Abortion, Habitual↗
PubMed1991

Visualization of altered myocardial lipids by 1H NMR chemical-shift imaging following ischemic insult.

Acute myocardial infarction is associated with an accumulation of lipids. Spectroscopic and chemical-shift imaging strategies which can depict the spatial distribution of these chemical species are evolving. The present study was undertaken to test whether the Dixon method could detect spatially lipids known to accumulate in myocardium after an ischemic insult. Seven dogs underwent a 24-h coronary artery occlusion (LAD = 4, Cx = 3). Post mortem, hearts were removed and imaged ex vivo. Myocardial samples were also evaluated by high-resolution 1H NMR spectroscopy. Lipid images revealed regions of increased signal intensity, in the regions corresponding to the myocardial infarction, particularly in the periphery of the infarction. An increase in mobile lipids was observed by 1H NMR spectroscopy of myocardial samples with moderately reduced blood flow and corresponding to regions with increased signal intensity on the lipid image. This study shows that chemical-shift imaging may be useful for detecting alterations in myocardial lipid levels following an ischemic insult.

Animals↗