Search PubMed⌕ Search

Biomedical subjects

R A Wilson

Publications and source records attributed to R A Wilson.

At least 181 records · Page 10Linked to original sources

Pulmonary leukocytic responses are linked to the acquired immunity of mice vaccinated with irradiated cercariae of Schistosoma mansoni.

Pulmonary cellular responses in C57BL/6 mice exposed to Schistosoma mansoni have been investigated by sampling cells from the respiratory airways with bronchoalveolar lavage. Mice exposed to cercariae attenuated with 20 krad gamma-radiation developed stronger and more persistent pulmonary leukocytic responses than animals exposed to equal numbers of normal parasites. Although vaccination with irradiated cercariae also stimulated T cell responses of greater magnitude and duration than normal infection, the lymphocytic infiltrate elicited by each regimen did not differ substantially in its composition, 5 wk after exposure. Studies with cercariae attenuated by different treatments established that a link exists between the recruitment of leukocytes to the lungs of vaccinated mice and resistance to reinfection. There was a strong association between pulmonary leukocytic responses and the elimination of challenge infections by vaccinated mice. Animals exposed to irradiated cercariae of S. mansoni were resistant to homologous challenge infection but were not protected against Schistosoma margrebowiei. Homologous challenge of vaccinated mice stimulated anamnestic leukocytic and T lymphocytic responses in the lungs, 2 wk postinfection, but exposure of immunized animals to the heterologous species failed to trigger an expansion in these populations of cells. Our studies indicate that pulmonary leukocytes and T lymphocytes are intimately involved in the mechanism of vaccine-induced resistance to S. mansoni. It remains unclear whether these populations of cells initiate protective inflammatory reactions against challenge parasites in the lungs, or accumulate in response to the activation of the protective mechanism by other means.

Animals↗

Isolation and characterisation of discoid granules from the tegument of adult Schistosoma mansoni.

Discoid granules were isolated from the tegument of adult Schistosoma mansoni by differential centrifugation of freeze-thaw extracts. Comparison of proteins and glycoproteins from discoid granules, surface membranes and the soluble fraction implied that discoid granules and the surface membrane were functionally linked. The results are discussed in terms of discoid granule function and surface membrane organisation.

Alkaline Phosphatase↗

Diazotised [125I]iodosulphanilic acid is not a marker for the outer bilayer of the tegument of adult Schistosoma mansoni.

Diazotised [125I]iodosulphanilic acid (DISA), has been used to label the tegument surface of adult male Schistosoma mansoni in vitro. In a surface membrane fraction prepared by freeze-thaw, only a negligible amount of lipid material was labelled by DISA, and 15 labelled protein bands were detected, ranging in apparent molecular weight from 21,000 to 175,000. As a result of experiments using digitonin to extract surface material, DISA has been described as a marker for the outer bilayer of the schistosome tegument surface. However, we found that two surface membrane fractions obtained by digitonin extraction, which were expected to be enriched in either outer or inner bilayer, yielded almost identical sodium dodecyl sulphate-polyacrylamide gel electrophoresis autoradiographic patterns, with 13 labelled protein bands (21 to 64 kDa) detected in each. In addition, a large proportion of the label was not bound firmly to the worm surface, and although the intact worm surface restricted the access of the label to membrane proteins, nevertheless proteins of the inner bilayer were labelled. Thus, we conclude that DISA is not a marker for the outer bilayer.

Alkaline Phosphatase↗

Antibody responses of rodents to a tegument membrane preparation from adult Schistosoma mansoni.

A preparation highly enriched in tegument membranes from adult worms has been used to probe rodent responses to schistosome surface antigens. All exposure regimens in mice stimulated levels of anti-tegument IgG, measurable by ELISA. Plateau levels of circulating antibody attained were similar after mixed-sex and male-only infections, and vaccination with tegument membranes. Female-only infections and exposure to irradiated cercariae stimulated lower levels of anti-tegument antibody. Responses in rats were similar, but occurred more rapidly, probably due to the large initial parasite exposure. Although both mice and rats could be stimulated to produce high levels of anti-tegument antibody by multiple vaccination, consistent protection against a challenge was not obtained. Paradoxically, rats and mice vaccinated with irradiated cercariae developed low levels of antibody to tegument membrane antigens but were highly resistant to challenge. It was concluded that, in the range of sera examined, antibody responses to schistosome tegument membranes did not correlate with the immune status of the host.

Animals↗

Antigen localization and the induction of resistance in mice vaccinated with irradiated cercariae of Schistosoma mansoni.

The fate of 75Se-labelled parasites and their released pre-synthesized macromolecules has been followed in three murine infection models. Parasite numbers in specific tissues were determined by autoradiography, and released material was estimated by gamma-counting of tissues, with adjustment for the presence of parasite-associated radiolabel. Marked differences were found between the three models. The pattern of migration of normal schistosomula was similar to that previously reported. In addition we have described the transit of parasites through the lymph nodes draining the infection site. Significant quantities of released material were detected in the skin, draining lymph nodes, bloodstream and liver. The circulating material was of parasite origin, macromolecular, and hence potentially antigenic. In comparison to the normal infection, radiation-attenuated parasites (inducing a high level of resistance to challenge) persisted in the skin, draining lymph nodes and lungs, releasing a proportionally greater amount of material in the nodes. In mice exposed to attenuated parasites and treated with the compound RO11-3128 at 24 h (inducing a low level of resistance) there was an early death and rapid clearance of the parasites whilst still in the skin. This situation resulted in the highest levels of released material in the skin, bloodstream and liver, but negligible levels in the draining lymph nodes. We suggest that the persistence of radiation-attenuated parasites in the skin and draining lymph nodes, together with the prolonged release of antigen in the latter site, compared to the normal situation, are major factors in the induction of resistance.

Animals↗

Observations on the implications of pathology induced by experimental schistosomiasis in baboons in evaluating the development of resistance to challenge infection.

Liver samples from 10 Schistosoma mansoni-infected baboons all yielded eggs but neither their egg counts nor duration of infection (less than 226 weeks) correlated with the slightly elevated liver collagen levels or minimal histological fibrosis observed. Approximately 10% of inert 9 and 15 micron diameter microspheres injected into the mesenteric veins of 2 baboons with acute, challenge S. mansoni infection reached their lungs (mainly 9 micron microspheres). Lung egg recoveries over 1000 were significantly less common among 175 baboons exposed once to S. mansoni infections than among 56 baboons exposed more than once. Among 221 S. mansoni-and S. haematobium-infected baboons, female worm, total tissue egg and lung egg recoveries were significantly correlated with each other but not with liver or (where available) spleen weights. Liver and spleen weights were strongly correlated with total body weight. Baboons did not develop significant liver fibrosis, even after prolonged schistosome infections. However, some liver 'leakiness' developed during acute primary and challenge infections, allowing small inert particles and eggs to pass to the lungs, but this 'leakiness' was not associated with resistance to challenge. In contrast to mice, such resistance in baboons cannot, therefore, be explained simply in terms of pathological changes due to previous infections.

Animals↗

Genetic evidence of clonal descent of Escherichia coli O157:H7 associated with hemorrhagic colitis and hemolytic uremic syndrome.

Genetic relatedness of 100 strains of Escherichia coli, isolated mostly from patients with hemorrhagic colitis or hemolytic uremic syndrome, was determined for chromosomal genotypes on the basis of allelic variation at 17 enzyme-encoding loci detected by multilocus enzyme electrophoresis. Fifteen of the 17 loci were polymorphic, with an average of 3.5 alleles per locus. Comparison of the observed combinations of alleles among strains revealed 25 distinct multilocus genotypes, which were used to define naturally occurring cell lineages or clones. Cluster analysis of the genotypic data revealed that isolates of serotype O157:H7 fall into a well-defined group of clonal genotypes that share alleles, on average, at 90% of their enzyme loci. The O157:H7 clonal group is only distantly related to other Verotoxin-producing strains belonging to other serotypes of E. coli. The results strongly support the hypothesis that isolates of E. coli O157:H7 obtained from geographically separate outbreaks and sporadic cases of hemorrhagic colitis and hemolytic uremic syndrome belong to a pathogenic clone that occurs throughout North America.

Alleles↗

An analysis of the haemodynamic effects of tolbutamide in conscious dogs.

1. In conscious chronically instrumented dogs, tolbutamide (5-45 mg/kg) induced significant dose-related increases in mean arterial pressure and left ventricular end-diastolic pressure. 2. Cardiac output was decreased while heart rate, d(LVP)/dt, and regional myocardial performance at the left ventricle were not significantly affected. Computed total peripheral resistance was increased. 3. Pretreatment with the alpha-antagonist phentolamine (1-1.5 mg/kg) abolished the pressor response. Furthermore, the pressor response to norepinephrine (0.1 microgram/kg) was enhanced by pretreatment with tolbutamide (45 mg/kg). 4. In an isolated tissue preparation using ring segments of canine femoral arteries, neither tolbutamide nor its major hepatic metabolites (carboxytolbutamide, p-toluene-sulfonamide and p-toluene-sulfonylurea) caused any smooth muscle contraction. However, pretreatment of these tissues with 10(-4), 10(-3), or 10(-2) mol/l tolbutamide potentiated the contractile response to norepinephrine by up to 19% and to phenylephrine by up to 8%. 5. It was concluded that the pressor effect of tolbutamide arises by potentiating the alpha-adrenoceptor mediated vasoconstrictor action of circulating endogenous catecholamines.

Adrenergic alpha-Antagonists↗

Genetic relationships among pathogenic strains of avian Escherichia coli.

Genetic relationships among 79 strains of Escherichia coli, isolated mostly from diseased chickens, were estimated on the basis of allelic variation at 15 enzyme-encoding loci, determined by multilocus enzyme electrophoresis. All 15 loci were polymorphic, with an average of 4.1 allelic states per locus. Comparisons of the observed combinations of alleles among strains revealed 37 distinct multilocus genotypes that were used to define naturally occurring cell lineages or clones. Two-thirds of the isolates were classified into 10 clones, including a single multilocus genotype that accounted for about a third of all isolates. For isolates of these clones, there was a high concordance (76%) between identity in multilocus genotype, O:K:H serotype, and pattern of resistance to five antibiotics. Cluster analysis disclosed two major complexes of closely related clones, in which more than 50% of the isolates were associated with localized infections (airsacculitis and pericarditis). Both complexes contained isolates with serotype O2:K1, indicating that this serotype can occur on diverse chromosomal backgrounds. The results suggest that colibacillosis within avian populations is caused by a relatively limited number of pathogenic clones representing at least two distinct clone complexes.

Alleles↗

Genetic relationships among pathogenic Escherichia coli of serogroup O157.

Escherichia coli strains of serotype O157:H7 are a newly described clonal pathogenic form associated with recent outbreaks of hemorrhagic colitis in humans. Although O157 strains of various H types have long been recognized as enterotoxigenic in animals, little is known about how these pathogenic animal strains are related to those of serotype O157:H7. To determine the genetic relatedness of O157:H7 isolates to animal O157 strains, we examined 194 O157 isolates, representing 12 distinct flagellar antigens (H serotypes), obtained from a variety of animal and human infections. To characterize isolates, we assayed allelic variation at 19 enzyme loci by multilocus enzyme electrophoresis. Genotypic comparisons of isolates revealed extensive variation among 33 distinct clonal genotypes that differed, on average, at 44% of the enzyme loci. K88 fimbriae were expressed in 72% of the isolates and occurred in a diversity of chromosomal genotypic backgrounds. Five major clonal groups were recognized; one group was clearly associated with porcine colibacillosis, and another was associated with human urinary tract infections. The O157:H7 genotype was not closely allied with any of the major groups of clones. The results indicate that O157 E. coli are genetically diverse and strongly suggest that the O157:H7 lineage was not recently derived from other pathogenic strains of the O157 serogroup.

Alleles↗

Phage typing set for differentiating Staphylococcus epidermidis.

A phage typing set composed of 13 phages is described for characterizing Staphylococcus epidermidis. Isolates (372) from cases of bovine mastitis were used in this study. Of these, 350 or 94% were successfully delineated, and 63 phage types were observed. Twenty two cultures were not typeable.

Animals↗

Long-term vasodilator therapy of chronic aortic insufficiency. A randomized double-blinded, placebo-controlled clinical trial.

Although vasodilator drugs acutely reduce regurgitation and improve cardiac performance in aortic insufficiency, their long-term effects on left ventricular size and function are uncertain. Consequently, we performed a double-blinded, placebo-controlled trial using hydralazine in 80 minimally symptomatic patients who had clinically stable, moderate-to-severe aortic insufficiency. Patients randomized to hydralazine displayed a progressive reduction in left ventricular end-diastolic volume index (LVEDVI) measured by radionuclide angiography, the predetermined end point of the study. At 24 months, mean LVEDVI had been reduced by 30 +/- 38 ml/m2, an 18% reduction from baseline. In contrast, LVEDVI changed minimally in patients randomized to placebo, and the intergroup differences over time were statistically significant (p less than 0.03). The hydralazine group also experienced reductions in left ventricular end-systolic volume index and increases in ejection fraction that were significantly different (both p less than 0.01) from changes in placebo-treated patients. These findings show that long-term treatment with hydralazine reduces the volume overload in aortic insufficiency and suggest that such therapy may have a beneficial effect on the natural history of the disease.

Administration, Oral↗

Examination of the mechanisms of pulmonary phase resistance to Schistosoma mansoni in vaccinated mice.

Potential mechanisms causing elimination of lung stage schistosomula were investigated in normal C57BL/6 mice and C57BL/6 mice previously vaccinated with irradiated cercariae. Autoradiography was used to measure the proportion of radiolabeled schistosomula which could be recovered from lung tissue by mincing and incubation. There was no difference between the two sets of mice at each time point, and no substantial diminution in the proportion recovered over the sampling period of 7 to 17 days post-infection. By this in vitro criterion, the emergence of schistosomula from lung fragments was not influenced by inflammation. However, we are unable to rule out the possibility that migration is impeded by inflammation in vivo. The migratory potential and viability of schistosomula recovered after residence in the lungs for increasing lengths of time was assessed by their introduction into the vasculature of naive recipients. The results indicate that significant numbers of schistosomula are capable of maturation, but fail to mature if left in situ in the lungs of both normal and vaccinated mice. No evidence was found that schistosomula suffer cytotoxic injury in the skin, subsequently dying in the lungs, or that they are damaged by the pulmonary inflammatory reactions which develop in vaccinated mice. Schistosomula delivered to the alveoli have a limited capacity to reenter tissues and mature. We suggest that in normal C57BL/6 mice the deflection of parasites into the alveoli during migration is the reason why many fail to mature. In vaccinated C57BL/6 mice a similar but augmented process may account for the elimination of a greater proportion of challenge parasites.

Animals↗

Strains of Escherichia coli associated with urogenital disease in dogs and cats.

Selected strains of Escherichia coli associated with urogenital disease in dogs and cats were evaluated for 3 virulence factors associated with human uropathogenic strains. Urogenital strains of E coli from dogs and cats had high prevalence of alpha hemolysin and were clustered in 5 to 10 somatic serogroups, attributes also shared by human uropathogenic strains. However, the canine and feline urogenital strains failed to have increased prevalence of mannose-resistant hemagglutination, as has been reported for human uropathogenic strains.

Animals↗

Effect of ribose on thallium-201 myocardial redistribution.

Myocardial 201Tl redistribution after transient ischemia may be too slow to allow identification of a reversible myocardial defect within the routine 201Tl imaging period. To determine whether 201Tl redistribution could be affected by a metabolic intervention, intravenous ribose was administered postischemia. Seventeen domestic swine were subjected to a 10-min ischemic period followed by either a 30-min i.v. ribose (n = 8) or saline (n = 9) infusion. Thallium-201 was injected during ischemia and myocardial 201Tl activity was continuously monitored in ischemic and nonischemic regions with miniature CdTe radiation detection probes. Coronary flow in the ischemic region was reduced to 25% of that in the nonischemic regions in both saline and ribose groups. The 201Tl time-activity curves demonstrated a significant enhancement of % 201Tl redistribution in the ribose-treated animals at the end of ribose infusion: Ribose (48 +/- 11%), Saline (20 +/- 4%), p less than 0.05. Alteration of 201Tl kinetics by ribose may permit earlier recognition of 201Tl myocardial redistribution after transient ischemia.

Animals↗

Effect of eating on thallium-201 myocardial redistribution after myocardial ischemia.

To determine whether eating a high-carbohydrate meal between initial and delayed postexercise thallium-201 (Tl-201) imaging affects detection of Tl-201 redistribution during exercise stress testing, 16 patients with stable angina performed 2 Tl-201 treadmill exercise stress tests within a 14-day interval. Immediately after initial postexercise imaging, patients either drank a commercially available instant breakfast preparation for the intervention test or drank an equivalent volume of water for the control test. Comparable exercise workloads were achieved by exercising patients to the same heart rate for both tests. The order of the 2 (intervention and control) tests were randomized. All patients had at least 1 region of Tl-201 myocardial redistribution on either their eating or control test scans, although only 7 of the 16 had positive treadmill exercise test responses. Forty-six regions showing Tl-201 myocardial redistribution were identified in all 144 regions examined. Significantly more of these regions were identified on control test scans than on eating test scans: 11 of 46 on both test scans, 6 of 46 only on eating test scans and 29 of 46 only on control scans (p less than 0.001). Consistent with results of the quantitative regional analysis, the percentage of Tl-201 clearance over 4 hours in the 46 Tl-201 myocardial redistribution regions was 39 +/- 8% for the eating tests and 29 +/- 8% for control tests (mean +/- standard deviation, p less than 0.003). In 4 patients diagnosis of transient ischemia would have been missed because their 14 Tl-201 myocardial redistribution regions were detected only on the control test scans.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Teflon granuloma mimicking a thyroid tumor.

An unusual case is presented of a patient who developed a "thyroid" nodule following injection of Polytef into the left posterior vocal cord for impaired phonation. Fine-needle aspiration cytology was interpreted as suspicious for malignant cells. Histological evaluation revealed a benign granulomatous lesion with numerous Teflon particles. Review of the literature relating to Teflon injections is presented.

Adult↗