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Biomedical subjects

R Wilson

Publications and source records attributed to R Wilson.

At least 469 records · Page 26Linked to original sources
PubMed1991

Quantitative prediction of human cancer risk from rodent carcinogenic potencies: a closer look at the epidemiological evidence for some chemicals not definitively carcinogenic in humans.

The existence of rodent carcinogens for which at least one epidemiological study found no evidence of human carcinogenicity has been claimed to provide evidence of the poor predictivity of rodent bioassays (F. K. Ennever, T. J. Noonan, and H. S. Rosenkranz (1987). Mutagenesis 2, 73-78). We have performed quantitative comparisons of the rodent and human carcinogenic potencies for these same chemicals. Starting with the rodent TD50 at the most sensitive site, we derived a predicted human incidence for the degree of exposure and duration of follow-up corresponding to the most comprehensive epidemiological study available, and then we compared the predicted incidence with the observed incidence. If a chemical produced no statistically significant increase in cancer at any site in the exposed population, consistency with rodent results is inferred if the minimum rodent TD50 is sufficiently high that no attributable cases would have been expected under the actual conditions of human exposure and follow-up. For 18 of the 22 chemicals examined, the human evidence is consistent with the predictions based on the rodent bioassay results. For two chemicals, dichlorobenzidine and ethylene thiourea, there is not enough epidemiological information to make a useful comparison with rodent bioassay data. For the two remaining chemicals, actinomycin D and vinylidene chloride, the human evidence is inconsistent with the predictions. But the conditions of the rodent bioassay of actinomycin D were inappropriate for the comparison, and for vinylidene chloride the human exposure dose and duration were uncertain; either chemical might yet demonstrate consistency with the rodent results in future epidemiological studies.

Algorithms↗
PubMed1991

Interaction of nontypable Haemophilus influenzae with human respiratory mucosa in vitro.

One laboratory strain (SH9) (n = 12) and five clinical isolates of unencapsulated Haemophilus influenzae replicated from 10(4) to 10(8) cfu/ml over 24 h in an organ culture of human respiratory mucosa in which only the intact mucosal surface is exposed. By transmission electron microscopy (TEM), bacteria were not seen in association with normal respiratory epithelium, even after incubation for 24 h. Histology and TEM morphometry demonstrated patchy and occasionally confluent damage to epithelia at this time, with bacteria associated only with cells that were structurally damaged. Scanning electron microscopy revealed an increased quantity of mucus in infected preparations; H. influenzae were associated with mucus by 14 h of incubation and with damaged epithelial cells by 24 h. Fimbriation of H. influenzae increased buccal cell adherence but did not facilitate association with normal respiratory epithelium and failed to increase epithelial damage or association with damaged cells. Epithelial damage may be prerequisite for association of H. influenzae with respiratory epithelium in vitro.

Bacterial Adhesion↗
PubMed1991

Interaction between Pseudomonas aeruginosa and Staphylococcus aureus: description of an anti-staphylococcal substance.

The presence of Pseudomonas aeruginosa in the sputum of 191 patients with cystic fibrosis was significantly related (p less than 0.0001) to the absence of Staphylococcus aureus. Cross-streaking tests showed that 40 of 50 clinical strains of P. aeruginosa produced substances that inhibited the growth of S. aureus. When incorporated into agar plates, this antibacterial substance(s) inhibited the growth of 177 of 189 strains of nine staphylococcal species, all of 16 methicillin-resistant S. aureus and 27 of 39 strains of six other gram-positive genera. The substance(s) did not inhibit 23 strains of seven gram-negative genera tested. The antibacterial activity was heat stable and could be extracted into chloroform; activity was retained on Sephadex G-15 (V/Vo approximately 2, Mr less than 500) and eluted as a single peak from high performance liquid chromatography, well separated from pseudomonic acid, pyocyanin and a number of other phenazines.

Anti-Bacterial Agents↗
PubMed1991

The effect of lithium therapy on parameters thought to be involved in the development of autoimmune thyroid disease.

This study has considered the effects of primary affective disorders and lithium therapy on a number of factors thought to be important in the development of autoimmune thyroid disease. These factors were examined in (a) controls with no history of any such disorders; (b) patients with primary affective disorders treated with drugs other than lithium and (c) patients with primary affective disorders treated with lithium alone. Eight of 40 patients who were receiving lithium therapy were found to be positive for thyroid microsomal and/or thyroglobulin antibodies, compared to only 3/40 patients who were receiving some other form of treatment for their depression. Peripheral blood mononuclear cells from patients receiving lithium were found to have significantly reduced numbers of suppressor/cytotoxic T cells (P less than 0.05). In addition, suppressor T cells from these patients showed a significantly reduced response to stimulation with concanavalin A (P less than 0.01). These effects were greatest in patients found to be antibody positive. Increased B cell activity, as measured by increased IgG and IgM release following mitogen stimulation, was seen in patients receiving lithium and in those patients receiving other forms of treatment for their depression. This would suggest that the increase is a feature of primary affective disorders and is not due specifically to lithium treatment. It would appear from this study that lithium therapy induces antibody formation in susceptible individuals and this may ultimately lead to the development of thyroid disease.

Adult↗
PubMed1991

The prevalence of severe mental handicap in Northern Ireland.

There are four administrative areas (Health and Social Services Boards) in Northern Ireland. Two prevalence surveys, carried out several years apart, show that there is a significant geographical gradient in the rates of severe mental handicap (IQ less than 50). The rates in the 20-29-year-old groups in the Eastern and Northern Boards range between 4.07 and 4.82 per thousand; comparable rates in the Southern and Western Boards range between 5.17 and 6.37. A similar gradient was discernible in the distribution of Down's syndrome.

Adolescent↗
PubMed1991

A clinical trial of red-cell concentrate prepared from blood collected in half-strength citrate anticoagulant.

Earlier studies have indicated that plasma from blood donations drawn into half-strength citrate anticoagulant (0.5 CPD-A2) may give improved yields of factor VIII:C after fractionation. It has also been shown previously that cellular components from blood donations drawn into 0.5 CPD-A2 have satisfactory in-vitro and in-vivo properties. The present study examines the clinical use of red cell concentrate (RCC) from 0.5 CPD-A2 blood donations. Forty-nine patients who were undergoing elective orthopaedic surgery and who required blood transfusion received 0.5 CPD-A2 RCC. A transfused control group of 107 patients received standard CPD-A1 RCC for their transfusion requirements. Patients in the two transfused groups had similar haemoglobin responses to transfusion. All patients experienced a moderate pyrexia following the operation. Both study groups showed similar responses to serum lactate dehydrogenase levels in the 2 weeks following surgery, and in postoperative peripheral blood platelet counts. Serious postoperative complications arose in both groups. In the 0.5 CPD-A2 group two patients had pulmonary emboli (one fatal) and one patient had a non-fatal myocardial infarction. Three patients had pulmonary emboli in the CPD-A1 transfused group. These incidences of major adverse events were within the expected range of these complications in patients who were undergoing major joint replacement surgery and did not differ significantly between the study groups. This study indicates that red cell concentrate prepared in half-strength citrate anticoagulant is comparable to that prepared in CPD-A1 for patients undergoing orthopaedic surgery.

Adenine↗
PubMed1991

Duration of action and effect on baroreflex function of the anti-arrhythmic alpha 1 antagonist UK-52,046.

The effects of acute and chronic oral administration of UK-52,046 (25 micrograms kg-1) on baroreflex function and its duration of action, were studied in conscious dogs. It was found that UK-52,046 had no effect on blood pressure and heart rate following acute and chronic administration. UK-52,046 shifted the phenylephrine dose response curve to the right, and the PE50 (measure of alpha 1-adrenoceptor antagonism) was increased (P less than 0.05) compared to placebo on day 1 (2, 4, 8 and 24 h) and day 8 (2, 4, 8 and 12 h). The antagonism was increased (P less than 0.05) on day 8 (0, 8 and 12 h) compared with day 1. Evaluation of the effects of UK-52,046 on baroreflex function using phenylephrine to increase blood pressure indicated no significant difference from placebo. It was concluded that at an antiarrhythmic dose, UK-52,046 has no effect on blood pressure, heart rate or baroreflex function. The pressor response curve was shifted to the right indicating a duration of action of at least 12 h on chronic oral administration.

Administration, Oral↗
PubMed1991

Effects of Bordetella pertussis infection on human respiratory epithelium in vivo and in vitro.

Bordetella pertussis infection probably involves attachment to and destruction of ciliated epithelial cells, but most previous studies have used animal tissue. During an epidemic, nasal epithelial biopsy specimens of 15 children (aged 1 month to 3 1/2 years) with whooping cough were examined for ciliary beat frequency, percent ciliation of the epithelium, and ciliary and epithelial cell ultrastructure. In addition, the in vitro effects of filtrates from a 24-h broth culture and of tracheal cytotoxin derived from B. pertussis on human nasal tissue organ culture were measured. B. pertussis was cultured from nasal swabs from 12 children. The mean ciliary beat frequency of their nasal biopsy specimens, 11.3 Hz (range, 10.4 to 13.0 Hz) was similar to that found in biopsy specimens from 10 normal children (mean, 12.5 Hz; range, 11.8 to 13.5 Hz). The abnormalities of the epithelium observed in 14 of 15 patients were a reduction in the number of ciliated cells, an increase in the number of cells with sparse ciliation, an increase in the number of dead cells, and extrusion of cells from the epithelial surface. In vitro, neither culture filtrate nor tracheal cytotoxin had any acute effect on ciliary function, but culture filtrate and tracheal cytotoxin (1 and 5 microM, respectively) caused extrusion of cells from the epithelial surface of turbinate tissue, loss of ciliated cells, an increased frequency of sparsely ciliated cells, and toxic changes in some cells. These changes were dose dependent and progressive, and between 36 and 90 h ciliary beating ceased. The observations made with patient tissue confirm that B. pertussis infection damages ciliated epithelium, and the in vitro experiments suggest that tracheal cytotoxin may be responsible for the abnormalities observed in vivo.

Bacterial Adhesion↗
PubMed1991

Stimulation of secretion into human and feline airways by Pseudomonas aeruginosa proteases.

We have investigated the effect of elastase and alkaline protease from Pseudomonas aeruginosa on airway secretion into the trachea of anesthetized cats and from human bronchial mucosa in vitro. Secretory macromolecules were radiolabeled biosynthetically with two precursors in the cat, [3H]glucose and [35S]sulfate, and with [35S]-sulfate only in human tissue. Both enzymes (2.6 x 10(-9) to 1.3 x 10(-6)M elastase and 8 x 10(-9) to 2.4 x 10(-6)M alkaline protease) released radiolabeled macromolecules in a concentration-dependent manner from the two preparations. Purified elastase, 1.3 x 10(-6)M, released radiolabeled macromolecules (delta 3H = +397 +/- 72%, delta 35S 225 +/- 40% over control, P less than 0.001) and periodic acid-Schiff- (PAS) reactive glycoconjugates (delta PAS = +4.1 +/- 0.96 micrograms/min or +102 +/- 20%; P less than 0.01) from cat trachea, as did alkaline protease, 2.4 x 10(-6)M (delta 3H = +356 +/- 57%, delta 35S = +176 +/- 25%, delta PAS = +7.5 +/- 1.3 micrograms/min or 194 +/- 36%, P less than 0.001). Increases in 3H exceeded those of 35S, suggesting surface epithelium as the main source of secretion. Inhibition of enzyme activity abolished secretory effects. Both enzymes also stimulated secretion from human bronchus (e.g., with elastase, 1.3 x 10(-6)M: delta 35S = +331 +/- 67%, delta PAS = +4.3 +/- 0.92 micrograms/min or +131 +/- 24%, P less than 0.001; with alkaline protease, 2.4 x 10(-6)M: delta 35S = +220 +/- 67%, delta PAS = +12.7 +/- 3.2 micrograms/min or +575 +/- 245%, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effects of human neutrophil elastase and Pseudomonas aeruginosa proteinases on human respiratory epithelium.

It has been suggested that proteinase enzymes could play an important role in the pathogenesis of chronic bronchial infections including bronchiectasis and cystic fibrosis (CF). Because Pseudomonas aeruginosa frequently colonizes the respiratory tract in bronchiectasis and CF, we examined the in vitro effects of human neutrophil elastase (HNE) and proteinase enzymes produced by P. aeruginosa (elastase: PE; alkaline proteinase: PAP) on the ciliary beat frequency (CBF) and ultrastructure of human nasal ciliated respiratory epithelium. HNE (500 micrograms/ml) progressively reduced CBF and caused marked epithelial disruption; lower concentrations (100 and 20 micrograms/ml) also caused epithelial disruption but without slowing CBF. The effects of HNE (500 micrograms/ml) were completely abolished by adding alpha 1-antitrypsin (5 mg/ml). There was no synergy between HNE and pyocyanin, a product of P. aeruginosa which slows CBF. PE in phosphate-buffered saline also caused epithelial disruption without slowing CBF; however, PE in medium containing divalent metal ions caused CBF slowing as well as epithelial disruption at 100 micrograms/ml. PAP (500 micrograms/ml) had almost no effect on ciliated epithelium. The effects of HNE and PE on nasal and bronchial epithelium obtained from the same patient were similar. Light and transmission electron microscopy revealed that HNE and PE were cytotoxic and caused detachment of epithelial cells from neighboring cells and the basement membrane. There was cytoplasmic blebbing of the cell surface and mitochondrial damage; however, no increase of abnormalities in the ultrastructure of cilia on living cells was seen. These results support the hypothesis that HNE and PE contribute to the delayed mucociliary clearance and epithelial damage that is observed in patients with chronic bronchial infection.

Bronchi↗
PubMed1991

Predicting the carcinogenicity of chemicals in humans from rodent bioassay data.

Regulatory agencies currently rely on rodent carcinogenicity bioassay data to predict whether or not a given chemical poses a carcinogenic threat to humans. We argue that it is always more useful to know a chemical's carcinogenic potency (with confidence limits) than to be able to say only qualitatively that it has been found to be a carcinogen. In a typical bioassay, a chemical is administered to groups of 50 to 100 rodents at the highest feasible level (the maximum tolerated dose) and rarely at less than 1/10 this dose in order to maximize the statistical significance of any increase in tumors that might result. Recently, much experimental work has focused on the mechanisms by which site-specific toxicity arising from chronic administration at the maximum tolerated dose may lead to carcinogenicity. Extrapolation of high-dose results to low doses does not take into consideration the possibility of a threshold dose, below which the carcinogenic potency is much lower or even zero. Threshold dose-response phenomena may be much more relevant to the etiology of cancer in the rodent bioassays than was earlier realized; if so, there is an even greater need for establishing dose-dependent potency estimates. The emphasis of this review is on the interspecies comparison of high-dose potencies. The qualitative and quantitative comparison of carcinogenicities between mice and rats and between rodents and humans is reviewed and discussed. We conclude that there is a good qualitative (yes/no) correlation for both the rat/mouse and the rodent/human comparison. There is also a good correlation of the carcinogenic potencies between rats and mice, and the upper limits on potencies in humans are consistent with rodent potencies for those chemicals for which human exposure data are available. For the rodent/human comparison, the best estimate of the interspecies potency factor is lognormally distributed around 1 when the potencies in both species are measured in units of (mg/kg-day)-1.

Animals↗
PubMed1991

[Not Available].

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Germany↗
PubMed1991

Efficacy of acyclovir against herpesvirus infection in Quaker parakeets.

We evaluated the efficacy of acyclovir against experimentally induced herpesvirus infection (Pacheco's parrot disease) in Quaker parakeets. Thirty-two of 40 birds were challenge-exposed with 0.1 ml of a suspension of herpesvirus (10(4) median cell culture infective doses [CCID50]) given IM. Treatment with acyclovir was started 24 hours later and was continued for 7 days. The birds were allotted to 5 groups of 8 birds each. There was a considerable difference in mortality between groups 1-5. Of 8 bird in each group, 6 died in group 1 (control), 1 died in group 2 (gavage), 3 died in group 3 (low dose, IM), 4 died in group 4 (high dose, IM), and none died in group 5 (contact controls). There was a significant (P = 0.023) difference in mortality between groups 1 and 2, thus the oral form of acyclovir administered by gavage was the most efficacious therapeutic regimen. Clinical signs and death occurred after discontinuation of acyclovir in groups 2 and 3, whereas the mean time of death for the control group was 6 days after challenge exposure. Herpesvirus was recovered by inoculation of chick embryo cell culture with pooled tissue suspensions from all birds that died. Histologic evidence of herpesvirus infection was found in most birds that died, with the control group having the most severe lesions. Surviving Quaker parakeets were transferred to cages with seronegative Quaker parakeets with no known exposure to herpesvirus. There have been no deaths attributable to herpesvirus infection in a period exceeding 2 years.

Acyclovir↗
PubMed1991

Temporal contrast sensitivity loss in primary open-angle glaucoma and glaucoma suspects.

The need for more sensitive tests for the early detection of compromised visual function in glaucoma is established by anatomic and psychophysical evidence of damage occurring to optic nerve fibers in eyes with normal visual fields. The results are reported of temporal frequency testing on 51 glaucoma suspects without visual field loss in either eye, 52 glaucoma patients with visual field deficits in the tested eye, and 11 normal subjects. Modulation transfer functions were obtained using a sinusoidally flickering 5 degrees spatially uniform white field viewed with central fixation and plotted at six frequencies from 5-30 Hz. The results showed a frequency-specific sensitivity loss centered at 15 Hz and a nonfrequency-specific mean sensitivity loss, that was greater, on average, in glaucoma patients than in suspects. Sensitivity losses of both kinds were seen in most glaucoma patients, but only in a minority of glaucoma suspects. About 12% of suspects were indistinguishable from the lowest performing one third of these glaucoma patients. A smaller number of suspects appeared to form a second mode in the frequency distribution for temporal sensitivity at 15 and 25 Hz. In patients with glaucoma, age was found to be a significant factor associated with the magnitude of mean sensitivity loss. Age was not a significant factor contributing to sensitivity loss in individual suspect data as measured by regression analysis, but it contributed to a small and consistent sensitivity loss across frequency for group-averaged data in those older than 55 years of age.

Adult↗
PubMed1991

Ciliary beat frequency and structure of recipient and donor epithelia following lung transplantation.

To investigate possible changes following lung transplantation, the structure and in vitro ciliary beat frequency (CBF) of airway epithelium from the cytology brushings of 9 heart-lung (HLT) and 5 single-lung (SLT) transplant recipients were examined. The CBF of brushings taken proximal and distal to the anastomosis was measured 2-10 months following transplant. There was no difference between the measured mean CBF at the two sites or between the two groups; HLT CBF: distal 11.0 +/- 0.5 Hz (standard error of mean), proximal 10.5 +/- 0.4 Hz, SLT CBF: distal 11.7 +/- 0.9 Hz, proximal 12.0 +/- 0.6 Hz. Mean CBF of bronchial brushings (except distal brushings from SLT patients) was significantly lower than that from controls: 13.6 +/- 0.3 Hz (n = 7) (p less than 0.05). Transmission electron microscopy of epithelial brushings from 4 patients (3 HLT, 1 SLT) revealed epithelial abnormalities both proximal and distal to the anastomosis, particularly ciliary depletion, mitochondrial abnormalities and death of cells. No significant ciliary ultrastructural abnormalities were seen in any tissue. We conclude that epithelial abnormalities were observed both proximal and distal to the anastomosis following lung transplantation. These may contribute to impairment of mucociliary clearance.

Bronchi↗