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Biomedical subjects

R Wilson

Publications and source records attributed to R Wilson.

At least 433 records · Page 24Linked to original sources
PubMed1992

Interaction of Haemophilus influenzae with mucus, cilia, and respiratory epithelium.

One nontypeable laboratory strain and five nontypeable clinical isolates of Haemophilus influenzae from sputum were investigated. Bacteria replicated from 10(4) to 10(8) cfu/ml over 24 h in an organ culture of human respiratory mucosa with only the intact mucosal surface exposed. By transmission electron microscopy, bacteria were not seen in association with normal respiratory epithelium, even after incubation for 24 h. H. influenzae infection caused patchy and occasionally confluent damage to epithelium, and the bacteria associated only with structurally damaged cells. Scanning electron microscopy revealed increased mucus, and slowed ciliary beat frequency was measured by photometry. Fimbriation of H. influenzae increased buccal cell adherence but did not facilitate association with normal or damaged respiratory epithelium or increase epithelial damage, indicating that adhesins other than fimbriae are present. Interactions with mucus, cilia, and epithelium are likely to be important in the pathogenesis of H. influenzae respiratory infections.

Cilia↗
PubMed1992

Enhanced release of elastase and oxidative inactivation of alpha-1-protease inhibitor by stimulated human neutrophils exposed to Pseudomonas aeruginosa pigment 1-hydroxyphenazine.

The in vitro effects of the Pseudomonas aeruginosa-derived phenazine pigments pyocyanin and 1-hydroxyphenazine (1-hp) on neutrophil elastase release and myeloperoxidase-induced inactivation of alpha-1-protease inhibitor (alpha 1-PI) were investigated. 1-hp (6-25 microM), but not pyocyanin, caused a dose-dependent enhancement of elastase release by FMLP:cytochalasin B (CB)-activated human neutrophils. 1-hp (0.78-6.25 microM) also increased the oxidative inactivation of the elastase inhibitory capacity of alpha 1-PI exposed to FMLP:CB-activated neutrophils. Methionine, a scavenger of hypochlorous acid, completely protected alpha 1-PI from inactivation by stimulated neutrophils in the presence or absence of 1-hp. Similar protective effects were observed with sodium azide, an inhibitor of myeloperoxidase. P. aeruginosa-derived 1-hp may promote an elastase-antielastase imbalance in vivo by increasing the release of neutrophil elastase and by enhancing the oxidative inactivation of alpha 1-PI, thereby contributing to the development of tissue destruction in P. aeruginosa-infected patients.

Humans↗
PubMed1992

2-Heptyl-4-hydroxyquinoline N-oxide, an antistaphylococcal agent produced by Pseudomonas aeruginosa.

Clinical isolates of Pseudomonas aeruginosa produce low molecular weight, hydrophobic substances which inhibit the growth of Staphylococcus aureus and other Gram-positive organisms. The active substances have been purified from a culture of P. aeruginosa and characterized as a mixture of 2-heptyl-4-hydroxyquinoline N-oxide and its homologues. The alkyl-hydroxyquinolines (derived through reduction of the N-oxide) were also produced by P. aeruginosa cultures but, in general, were less active against S. aureus. 2-Heptyl-4-hydroxyquinoline was identified in a sample of human bronchial secretions from a patient with cystic fibrosis who was heavily colonized with P. aeruginosa. Production of antibacterial alkyl-hydroxyquinoline N-oxides in human lung may explain the observation that the presence of P. aeruginosa in the sputum of patients with cystic fibrosis is correlated with the absence of S. aureus.

Chromatography, High Pressure Liquid↗
PubMed1992

Fourier transform infrared microspectroscopy is a new way to look at plant cell walls.

Highly reproducible Fourier transform infrared (FTIR) spectra from both single onion (Allium cepa) cell walls and their constituent polymers were obtained under a variety of sampling conditions. The specificity of the chemical extraction sequence used in the preparation of the material was confirmed: pectins only are extracted by cyclohexanediaminetetraacetic acid and sodium carbonate, whereas xyloglucans are extracted by increasing concentrations of potassium hydroxide. There was very little contamination of the first potassium hydroxide extract with residual pectin. The low abundance of both phenolics and protein was also confirmed. The first sodium carbonate extraction almost completely removes esters remaining in the cell wall. We have demonstrated that FTIR spectroscopy can detect large conformational changes in pectic polymers on removal from the cell wall and on drying. FTIR spectroscopy provides a powerful and rapid assay for wall components and putative cross-links by identifying polymers and functional groups nondestructively in muro. The availability of micro-sampling and data acquisition techniques that permit subtraction of the blanket absorption of water make FTIR spectroscopy particularly suitable for studies of cell wall architecture. The use of polarizers with the microscope accessory permits determination of the orientation of particular functional groups with respect to the direction of cell elongation in carrot suspension cells.

Journal Article↗
PubMed1992

Spin echo nuclear magnetic resonance studies on intact erythrocytes: changes in cellular metabolism as a consequence of carbimazole therapy.

OBJECTIVE: Because the exact mechanism of action of carbimazole is uncertain, nuclear magnetic resonance (NMR) spectroscopy was used to investigate cellular changes in erythrocytes from Graves' patients following a course of carbimazole therapy. DESIGN: NMR spectroscopy was carried out using intact erythrocytes obtained from Graves' patients prior to and at 2 and 12 months after carbimazole treatment. The data were correlated with thyroid hormone and antibody levels. PATIENTS: Twenty patients (four males; 16 females) with newly diagnosed and previously untreated Graves' disease were enrolled into the study. Assessments were made prior to the commencement of therapy and after 2 and 12 months on treatment. Of the 20 patients assessed at 0 and 2 months only 12 completed the study. MEASUREMENTS: The oxidation-reduction balance of erythrocyte glutathione was measured directly using 1H spin echo NMR spectroscopy of intact cells. Thyroid hormone and antibody levels were measured using reported methods. RESULTS: At 2 and 12 months a significant (P < 0.01) oxidation of the erythrocyte glutathione was observed. Of the four thyroid related markers (T3, T4, TRAb and TSH) assessed in this study both T3 (P < 0.001) and TRAb (P < 0.001) were observed to correlate with the NMR observed changes in glutathione. However, in-vitro experiments indicated that carbimazole does not affect red cell glutathione directly. CONCLUSIONS: A model is presented which uses the hydrated iodium cation (I+), the natural product of T4 conversion to T3, as a chemical oxidant which can produce the observed clinical alteration in intracellular glutathione in ex-vivo erythrocytes. It is suggested that a major factor in the action of carbimazole in Graves' disease may be to stimulate the function of the deiodinase enzymes.

Adult↗
PubMed1992

Thyroid function tests are rarely abnormal in patients with severe hyperemesis gravidarum.

OBJECTIVES: There is considerable controversy in the literature as to the cause of hyperemesis gravidarum. The aim of this project was to measure a range of thyroid hormone levels in a group of hyperemetic pregnant women. PATIENTS: The study was carried out in 10 first trimester pregnant women with hyperemesis gravidarum. All had been admitted to hospital due to the severity of their symptoms. Fifty age matched, healthy first trimester pregnant women were used as controls. MEASUREMENTS: Blood samples from the women were analysed for total T3 (TT3), total T4 (TT4), free T4 (FT4), TSH, thyrotrophin receptor antibodies (TRAb), thyroid stimulating antibodies (TSAb) and thyroid microsomal and thyroglobulin antibodies. Human chorionic gonadotrophin (hCG) levels were also measured. RESULTS: While individual patients were found to have some abnormal thyroid function tests the group as a whole showed no consistent pattern of abnormality and did not differ significantly from a group of healthy first trimester pregnant women. hCG levels were also within the normal range in the hyperemetic patients. DISCUSSION: None of the women in this study received any antithyroid medication and their symptoms improved as the pregnancy progressed. These results would suggest that there is no underlying thyroid abnormality in patients with hyperemesis gravidarum. It would appear that neither thyroid hormones, nor hCG contribute to the pathogenesis of the condition.

Antibodies↗
PubMed1992

Comparison of the dependence of the TD50 on maximum tolerated dose for mutagens and nonmutagens.

The relationship between the minimum TD50 (i.e., the TD50 measured at the most sensitive site) and the maximum dose administered (maxD) in rodent carcinogenicity bioassays was investigated separately for mice and rats. The relationship between log(1/TD50) and log(1/maxD) was analyzed as a function of (1) mutagenicity and (2) the statistical significance cutoff for selecting the minimum TD50 values. For rat bioassays, the variance of log(1/TD50) is larger and the correlation of log(1/TD50) with log(1/maxD) is weaker for mutagens than for nonmutagens, suggesting that the relationship between minimum TD50 and MTD is, in general, stronger for nonmutagens than for mutagens. The difference in correlation does not depend on the TD50 statistical significance cutoff, but the difference in variance is not significant for the most stringently selected dataset. For mouse bioassays, no significant mutagen/nonmutagen differences in log(1/TD50) variance are found. A significantly weaker correlation of log(1/TD50) with log(1/maxD) for mutagens in comparison to nonmutagens occurs only for the dataset with minimum TD50 chosen at the least stringent level, suggesting that this difference may be due to chance variation. We also looked for changes in correlation and regression parameters as a function of mutagenic potency in Salmonella; the variance of log(1/TD50) and its correlation with log(1/maxD) are not found to vary in a consistent manner. Taken as a whole, our results indicate that (1) mutagenicity is a determinant of the TD50/maxD relationship in rats and (2) any effect that mutagenicity may exert on the TD50/maxD relationship in mice is unimportant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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↗