Search PubMed⌕ Search

Biomedical subjects

R A Wilson

Publications and source records attributed to R A Wilson.

At least 127 records · Page 7Linked to original sources
PubMed1993

Phenotypic and functional properties of Th lines and clones recognizing larval antigens of Schistosoma mansoni.

Five T cell clones and two lines were derived from the lymph nodes (LN) of C57BL/6 mice immunized with radiation-attenuated lung-stage larvae of Schistosoma mansoni. All seven clones/lines were CD4+, CD8- and expressed high levels of CD44 and CD45RB surface markers. After prolonged maintenance in-vitro, with soluble antigen from 18 h schistosomula (SSP), five retained the ability to proliferate readily and release IFNg in response to concanavalin A (Con-A) and to SSP and/or soluble adult worm antigen (SWAP). These Th clones/lines induced significant footpad DTH reactions when injected with SWAP, but were unable to confer protective immunity after transfer to naïve recipient mice. This result could be explained by the antigen specificity of the clones/lines, since they were not able to release IFNg when cultured in-vitro with living lung-stage larvae. A second possibility is that the high level of CD45RB expression, which is not seen on the surface of pulmonary CD4+ memory/effector cells isolated directly from protectively-vaccinated mice, alters the ability of the clones/lines to release IFNg and to induce a DTH response in the lungs when they encounter antigen released from migrating schistosomula.

Animals↗
PubMed1993

Clonal relationships among Escherichia coli strains that cause hemorrhagic colitis and infantile diarrhea.

The genetic relationships among 1,300 isolates of Escherichia coli representing 16 serotypes associated with enteric disease, including O157:H7 strains recovered from patients with hemorrhagic colitis and hemolytic uremic syndrome and O26:H11, O55:H6, O55:H7, O111:H2, and O128:H2 strains, many of which were isolated originally from infants with diarrhea, were estimated from allelic variation among 20 enzyme-encoding genes detected by multilocus enzyme electrophoresis. Multiple electrophoretic types were observed among isolates of each serotype, with isolates of the same O serogroup differing on average at 28% of the enzyme loci. Comparisons of the multilocus enzyme profiles revealed that 72% of the isolates belong to 15 major electrophoretic types, each of which corresponds to a bacterial clone with a wide geographic distribution. Genetically, the O157:H7 clone is most closely related to a clone of O55:H7 strains that has long been associated with worldwide outbreaks of infantile diarrhea. We propose that the new pathogen emerged when an O55:H7-like progenitor, already possessing a mechanism for adherence to intestinal cells, acquired secondary virulence factors (Shiga-like cytotoxins and plasmid-encoded adhesins) via horizontal transfer and recombination.

Alleles↗
PubMed1993

Characterization of enterotoxigenic Escherichia coli isolated from U.S. troops deployed to the Middle East.

Enterotoxigenic Escherichia coli (ETEC) was a common cause of traveler's diarrhea in U.S. soldiers in the Middle East in 1989 and 1990. To determine which bacterial components would be useful in a vaccine, potential protective antigens (toxin, colonization factor antigen [CFA], and serotype) from 189 ETEC isolates were examined. Nearly half of the isolates expressed both ETEC toxins, 39% had only heat-stable enterotoxin (ST), and 17% had heat-labile enterotoxin (LT). CFA/I was the least common colonization factor antigen (11%), CFA/II was common (34%), as was CFA/IV (31%), and 24% expressed none of these CFAs. Fifty-seven O:H serotypes were found. Serotype O6:H16 was the most common, occurring in 29% of the ETEC isolates, usually with LT-ST and CFA/II. Generally, CFA/II was associated with expression of both toxins, CFA/IV was associated with expression of ST, and none of the CFAs was routinely found with LT. We conclude that ETEC from soldiers in the Middle East expressed a variety of antigens and that an effective vaccine will require multiple protective antigens.

Antigens, Bacterial↗
PubMed1993

Irradiation of Schistosoma mansoni cercariae impairs neuromuscular function in developing schistosomula.

Optimally attenuated larvae of Schistosoma mansoni (20 krad) are incapable of migrating farther than the lungs, and they induce high levels of resistance in mice to a subsequent challenge infection. The effect of gamma radiation on the parasite is described and related to the migratory pattern of attenuated larvae. Scanning electron microscopy revealed marked morphological differences between normal and irradiated larvae at the lung stage of development. The latter exhibited random constrictions, probably resulting from contraction of circular muscle fibers, at intervals along the length of the body and showed subtle differences in motility. We suggest these abnormalities account for persistence of attenuated larvae in the skin-draining lymph nodes and lungs, 2 events that are instrumental to the induction of protective immunity in this vaccine model.

Animals↗
PubMed1992

Monoclonal antibody to IFN-gamma modifies pulmonary inflammatory responses and abrogates immunity to Schistosoma mansoni in mice vaccinated with attenuated cercariae.

In C57Bl/6 mice vaccinated with a single dose of attenuated cercariae of Schistosoma mansoni, the major site of immune elimination of intact challenge parasites is the lungs. The effector mechanism involves the formation of focal inflammatory responses throughout the pulmonary tissues. These foci are rich in CD4+ T cells, believed to be memory:effector cells of the Th1 type. To investigate the role of IFN-gamma in these inflammatory responses, vaccinated mice were treated with neutralizing mAb. Administration on days 4, 8, 12, and 16 post-challenge, the period over which elimination of challenge parasites takes place in the lungs, gave an average 89.5% abrogation of protective immunity. Analysis of pulmonary cell populations recovered by bronchoalveolar lavage from treated nonimmune mice at day 14 post-challenge revealed a sharp increase in pulmonary eosinophilia, relative to intact vaccinated and challenged animals. The inverse relationship between eosinophilia and protection suggests that eosinophils do not play a vital role in the immune effector mechanism in this model. Pulmonary foci of treated mice were larger, less compact, and of different cellular composition from those of control groups. They contained increased numbers of eosinophils, together with numerous multinucleated giant cells. The effects observed in the anti-IFN-gamma mAb-treated mice, together with the maintenance of MHC class II expression on alveolar macrophages in these animals, could all be explained by the production of IL-4 and other Th2 cytokines. Thus, neutralization of IFN-gamma during challenge responses may shift the Th balance towards domination by the Th2 subset.

Animals↗
PubMed1992

Correlates of aortic distensibility in chronic aortic regurgitation and relation to progression to surgery.

Aortic distensibility decreases with increasing age. Patients with chronic aortic regurgitation eject a large stroke volume into the proximal aorta. A decrease in distensibility of the aorta may impose a higher afterload on the left ventricule and may contribute to deterioration of left ventricular function over time. Accordingly, aortic distensibility was measured in 33 patients aged 13 to 73 years who had chronic isolated aortic regurgitation with minimal or no symptoms. Ascending aortic diameter was measured 4 cm above the aortic valve by two-dimensional echocardiography and pulse pressure was measured simultaneously by sphygmomanometry. Aortic distensibility was calculated as (Change in aortic diameter between systole and diastole/End-diastolic diameter)/Pulse pressure. Left ventricular systolic wall stress and mass were derived from standard M-mode echocardiographic measurements. Left ventricular volumes and ejection fraction were measured by radionuclide ventriculography. Aortic distensibility decreased logarithmically with increasing age (r = -0.62, p less than 0.001) and also correlated inversely with systolic wall stress, left ventricular mass and end-diastolic volume. Patients who eventually underwent aortic valve replacement for symptoms of left ventricular dysfunction had significantly lower aortic distensibility than did those who did not yet require valve replacement: 0.09 +/- 0.08 vs. 0.22 +/- 0.19 x 1/100 (1/mm Hg) (p less than 0.05). Thus, the reduced aortic distensibility that occurs with increasing age may contribute to the gradual left ventricular dilation and dysfunction seen in patients with chronic aortic regurgitation.

Adult↗
PubMed1992

T cell-derived cytokines associated with pulmonary immune mechanisms in mice vaccinated with irradiated cercariae of Schistosoma mansoni.

In C57Bl/6 strain mice vaccinated with attenuated cercariae of Schistosoma mansoni, the major site of immune elimination of normal challenge parasites is the lungs. The immune effector mechanism involves formation of focal inflammatory responses; the abundance of CD4+ T cells and the activation of alveolar macrophages suggests a role for inflammatory cytokines. We report the profile of cytokines produced by cultures of leukocytes recovered by bronchoalveolar lavage (BAL) from the lungs of vaccinated and challenged mice. From 14 days after vaccination, BAL cultures contained infiltrating lymphocytes that produced abundant quantities of IFN-gamma and IL-3 on stimulation with larval Ag. Production declined from day 21 although the infiltrate of lymphocytes persisted. Challenge of vaccinated mice resulted in a second influx of IFN-gamma and IL-3-producing cells, earlier than after vaccination or in the appropriate controls. Ablation studies revealed that CD4+ T cells were essential for the production of IFN-gamma. The timing of cytokine production after vaccination, and challenge was coincident with the phases of macrophage activation previously reported. At no time could lymphocytes in BAL cultures be stimulated to proliferate with either larval Ag or mitogen, in contrast to splenocytes from the same mice. Furthermore, T cell growth factor activity was not detected in BAL cultures stimulated with Ag. We suggest that the lymphocytes recruited to the lungs are memory/effector cells. When Ag released from challenge schistosomula is presented to these cells, they respond by secreting cytokines that mediate the formation of cellular aggregates around the parasites, blocking their onward migration.

Animals↗
PubMed1992

In vivo lymphocyte responses in the draining lymph nodes of mice exposed to Schistosoma mansoni: preferential proliferation of T cells is central to the induction of protective immunity.

The in vivo cellular responses associated with the induction of specific immunity by attenuated larvae of Schistosoma mansoni in mice have been investigated. Using in vivo 5-bromo-2'-deoxyuridine incorporation, the changes in cell proliferation in the skin- and lung-draining lymph nodes (LN) of vaccinated animals were measured. A marked increase in the number of dividing cells was detected in both groups of LN, with a preferential increase in the proportion of proliferating T, relative to B, lymphocytes. Several dynamic components of cell migration have been examined to assess their relative contribution to the overall changes in the LN of immunized mice. It was determined that a significant part of the observed accumulation of cells is due to the effect of hyperaemia. There was no alteration in the affinity of the LN for T and B lymphocytes, but we concluded that the majority of recruited B cells failed to exit the nodes. The results have highlighted the importance of T cell proliferation within the draining LN for the successful immunization of mice with attenuated parasites.

Animals↗
PubMed1992

Cross-reactivity between Necator americanus and Schistosoma mansoni in mice.

Poly-parasitism is common in endemic communities and reactivity of sera from hookworm-infected patients against schistosomular antigens has been reported. Protective cross-immunity between N. americanus and S. mansoni was investigated in NIH and BALB/c mice. Protective resistance to homologous challenge with both parasites was confirmed in this model, however, functional immunity to heterologous challenge was not demonstrated. Sera from animals which had received homologous challenge with N. americanus and from hookworm-infected mice, which had previously been exposed to radiation-attenuated S. mansoni, exhibited an enhanced IgGAM response to infective stage N. americanus somatic antigens. The implications of these results with respect to serodiagnosis are discussed.

Animals↗
PubMed1992

The role of mononuclear-cell recruitment to the lungs in the development and expression of immunity to Schistosoma mansoni.

The role of pulmonary cellular responses in the induction and expression of immunity to Schistosoma mansoni has been evaluated. From experiments in which mice were challenged at intervals after vaccination, we conclude that the resistance mechanism operating in the lungs develops between days 11 and 20. Injection of 51Cr-labelled splenocytes revealed that mononuclear cell recruitment to the lungs, stimulated by the arrival of attenuated schistosomula, intensified progressively between days 10 and 16 post-vaccination. The increased cellularity was reflected in a 19.5% augmentation in the wet-weight index (WW). The period of enhanced cell recruitment therefore coincided with the build-up of resistance. By day 22 post-vaccination infiltration had declined, whilst WW remained elevated. This indicates the persistence of recruited cells, which include schistosome-reactive T lymphocytes, in the lungs. We were unable to demonstrate augmented recruitment of 51Cr-labelled cells after challenge of vaccinated mice, but WW rose slightly, peaking on day 12. Although clearly of a lower order than the primary response, the secondary response was more rapid, implying the existence of immunological memory. These results accord with the concept that schistosome-reactive T lymphocytes recruited after vaccination 'arm' the lungs against the arrival of challenge parasites.

Animals↗
PubMed1992

Distribution and characteristics of verocytotoxigenic Escherichia coli isolated from Ontario dairy cattle.

Faecal swabs obtained from a random sample of 1131 cows and 659 calves on 100 southern Ontario dairy farms were examined for verocytotoxigenic Escherichia coli (VTEC) using a Vero cell assay. Five isolates from each positive culture were tested similarly. Positive colonies were examined with DNA probes for Shiga-like toxin I (SLT-I) and SLT-II sequences. Probe-negative colonies were tested for neutralization of verocytotoxicity using anti-SLT-I and anti-SLT-IIv antisera. Colonies showing no neutralization response were examined in a polymerase chain reaction procedure. Colonies positive by any test were confirmed to be E. coli biochemically, serotyped, biotyped and tested for antimicrobial resistance. Faecal culture supernatants which were positive in the Vero cell assay, but culture negative, were examined using the neutralization assay. Animals were classified positive by faecal culture supernatant or by positive VTEC isolate. The prevalence rates of VTEC infection in cows and calves were estimated to be 9.5 and 24.7%, respectively. The proportion of animals infected on each farm ranged from 0 to 60% for cows and 0 to 100% for calves. Of 206 VTEC isolates identified, few were of serotypes which have been isolated from humans and none were E. coli O 157.H7.

Animals↗
PubMed1992

Murine intestinal humoral responses in chronic Schistosoma mansoni infections.

Specific and non-specific production of immunoglobulins (Ig) by the intestinal mucosa was examined in mice infected with the human blood fluke Schistosoma mansoni. Ileal and colonic mucosal tissue samples were cultured for 2 days, the medium replaced and the culture continued for a further 2 days. Ig concentrations and specific antibodies to soluble schistosome egg antigens in culture supernatants were estimated by isotype-specific ELISA. Cultured mucosae from control mice produced little IgG, but significant amounts of IgA and IgM on prolonged culture. IgG concentrations were increased in infected animals, mainly in the initial culture period, indicative of systemic, rather than local origins. By contrast, significantly increased local production of IgA and IgM occurred after the start of egg deposition in the intestinal mucosae. Although specific anti-egg antibodies of the IgG and IgM class were detected, none of the local IgA response was specific for schistosome eggs. We conclude that specific intestinal immune responses to schistosome eggs reflect systemic responses, whereas locally increased IgA production is largely non-specific. This pattern of response is likely to be related to the prior systemic exposure to schistosome eggs, which results in polyclonal local B-cell activation, but fails to trigger an antigen-specific IgA mucosal response.

Animals↗
PubMed1992

Intravascular ultrasonic assessment of lumen geometry and distensibility of the angiographically normal artery: a correlation with quantitative angiography.

The feasibility of assessing lumen diameter and area using a 30-MHz mechanically driven ultrasound imaging device was evaluated in vitro in phantoms and in vivo in eight human arteries (six iliac, two brachial). Ultrasound data were compared to angiographic data derived from the cardiovascular angiographic analysis system. In addition, the change of lumen area in a given cardiac cycle was determined in each patient. A close relation between ultrasound and angiography was observed in the phantom studies. In the first three patients there was disagreement; ultrasound images showed larger values compared to the angiographically derived values. Disagreement was related to the use of nominal measurements of the sheath supplied by the manufacturer as calibration. Data on the five other patients showed a close relation between the values derived with ultrasound and angiography. The arterial lumen area revealed a 5% +/- 2% change during one cardiac cycle. The intra- and interobserver variability test showed good correlation for the ultrasound study. This study demonstrates that intravascular ultrasound is an accurate and reproducible technique to measure vascular diameter, lumen area, and arterial wall distensibility in vivo.

Adult↗
PubMed1992

Outer membrane protein patterns mark clones of Escherichia coli O2 and O78 strains that cause avian septicemia.

Major outer membrane proteins were isolated from 36 Escherichia coli strains representing six common clones of the O2 and O78 serogroups implicated in avian colisepticemia. Clonal relationships among isolates were inferred from an analysis of polymorphism at 20 enzyme-encoding loci detected by multilocus enzyme electrophoresis. For isolates of these clones, there was a high concordance (greater than 90%) between identity in multilocus genotype and major outer membrane protein patterns. The results indicate that major outer membrane protein patterns discriminate among the genetically different clonal groups that constitute the heterogeneous O2 and O78 serogroups associated with avian disease.

Alleles↗
PubMed1992

Effect of balloon angioplasty on femoral artery evaluated with intravascular ultrasound imaging.

BACKGROUND: Intravascular ultrasound was used to assess the immediate effect of balloon angioplasty on the superficial femoral artery. METHODS AND RESULTS: In 16 consecutive patients, corresponding ultrasonic cross sections (n = 72) before and after balloon angioplasty were qualitatively and quantitatively analyzed. The qualitative data were compared with angiographic findings. Before intervention, the angiographically demonstrated obstructive lesions were confirmed by intravascular ultrasound. Ultrasound enabled discrimination between soft (n = 43) and hard (n = 29) lesions, as well as between eccentric (n = 57) and concentric (n = 15) lesions. After balloon angioplasty, the presence of a dissection assessed angiographically in 14 patients was confirmed by intravascular ultrasound. Additional morphological information provided by ultrasound included plaque rupture in 14 patients and internal lamina rupture in six patients. Quantitative ultrasound data revealed an increase in free lumen area from 9.7 +/- 4.7 to 18.3 +/- 7.0 mm2 (p less than or equal to 0.01), an increase in minimal lumen diameter from 2.8 +/- 0.7 to 3.6 +/- 1.2 mm (p less than or equal to 0.01), and an increase in media-bounded area from 21.7 +/- 5.4 to 28.3 +/- 5.8 mm2 (p less than or equal to 0.01). The lesion area for the majority of cases (n = 32) remained unchanged (13.0 +/- 4.9 mm2 versus 12.9 +/- 4.6 mm2), or the lesion disappeared partially (from 9.1 +/- 0.9 to 4.3 +/- 1.4 mm2, n = 4, p less than or equal to 0.01) or totally (from 10.1 +/- 4.2 to 0 mm2, n = 6). Stretching of the arterial wall was further evidenced by medial thinning from 0.55 +/- 0.19 to 0.34 +/- 0.11 mm (p less than or equal to 0.01). CONCLUSIONS: Luminal enlargement by balloon dilatation is achieved primarily by overstretching the arterial wall, with the lesion volume remaining practically unchanged. Overstretching is accompanied almost always by dissection and plaque rupture and occasionally by an internal lamina rupture.

Aged↗
PubMed1992

T cell derived cytokines in lung-phase immunity to Schistosoma mansoni.

In C57Bl/6 strain mice vaccinated with radiation-attenuated cercariae of Schistosoma mansoni immune elimination of challenge parasites occurs in the lungs. Leucocytes were recovered from the lungs of such mice by bronchoalveolar lavage and cultured in vitro with larval antigen; the profile of cytokines released was then analyzed. From 14 days after vaccination, BAL cultures contained infiltrating lymphocytes which produced abundant quantities of IFN-g and IL-3. Challenge of vaccinated mice resulted in a second influx of IFN-g and IL-3--producing cells, earlier than after vaccination or in the appropriate controls. Ablation studies revealed that CD4+ T cells were the source of IFN-g. The timing of cytokine production after vaccination, and challenge was coincident with the phases of macrophage activation previously reported. At no time could lymphocytes in BAL cultures be stimulated to proliferate with either larval Ag or mitogen, in contrast to splenocytes from the same mice. Furthermore, T cell growth factor activity was not detected in BAL cultures stimulated with Ag. We suggest that the lymphocytes recruited to the lungs are memory/effector cells. When Ag released from challenge schistosomula is presented to these cells, they respond by secreting cytokines which mediate the formation of cellular aggregates around the parasites, blocking their onward migration.

Animals↗