Biomedical subjects

R A Wilson

Publications and source records attributed to R A Wilson.

At least 19 recordsLinked to original sources

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

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↗

PubMed1992

Extrinsic compression of the superficial femoral artery at the adductor canal: evaluation with intravascular sonography.

Balloon angioplasty of the superficial femoral artery was performed in 15 consecutive patients with obstructive atherosclerotic disease near the adductor hiatus. After angioplasty, extrinsic compression of the femoral artery at the adductor hiatus was shown on intravascular sonograms in five patients (33%). In retrospect, this inward deformation of the arterial wall was thought to be present in only one case before angioplasty. After angioplasty, intravascular sonography was used successfully to differentiate between residual stenosis due to residual plaque and that due to extrinsic compression of the wall of the femoral artery near the adductor hiatus. We conclude that intravascular sonography may be a useful adjunct to angiography for determining the cause of residual stenosis.

Angioplasty, Balloon↗

PubMed1992

Susceptibility of Escherichia coli isolated from intramammary infections to phagocytosis by bovine neutrophils.

Thirteen Escherichia coli isolated from naturally occurring IMI were tested for susceptibility to phagocytosis by bovine blood neutrophils. Isolates were opsonized in pooled serum collected from nine healthy lactating cows. Bacteria isolated from IMI first diagnosed within 3 d after calving were more resistant to phagocytosis than were isolates from IMI originating during either the first half of the dry period or later during lactation. Duration of the IMI was negatively correlated with both phagocytic index and percentage of neutrophils phagocytizing within bacterial isolates from IMI originating at calving and during lactation. Phagocytosis was independent of duration of IMI within isolates from IMI originating during the first half of the dry period. Susceptibility to in vitro phagocytosis by neutrophils was not related to O antigen serotype, encapsulation, or growth in dry cow secretion.

Animals↗

PubMed1992

The generation of interferon-gamma-producing T lymphocytes in skin-draining lymph nodes, and their recruitment to the lungs, is associated with protective immunity to Schistosoma mansoni.

We have examined immunological responses in the skin-draining lymph nodes (SLN) and lungs of mice during the 3 weeks after percutaneous exposure to attenuated larvae of Schistosoma mansoni. Cercariae irradiated with 20 krads (V20) were highly protective and sustained an increased number of CD4+ T cells in the SLN. On secondary exposure to schistosome antigen in vitro, these cells were capable of proliferating and secreting high levels of interferon-gamma (IFN-gamma) and interleukin-3 (IL-3). However, in mice exposed to non-protective 80 krad-irradiated (V80) cercariae, secretion of these cytokines occurred early and only transiently. Significantly elevated numbers of CD4+ T lymphocytes were recoverable on Day 21 from the lungs of V20, but not V80 mice. These cells secreted high levels of IFN-gamma and IL-3 in vitro, but not IL-2 and IL-4. Mice immunized intravenously with attenuated lung-stage schistosomula were not protected, despite having an elevated pulmonary lymphocyte population. Moreover these cells failed to secrete IFN-gamma and IL-3. However, significant protection was achieved where exposure of mice to a combination of V80 cercariae and lung-stage schistosomula resulted in the recruitment of IFN-gamma secreting cells to the lungs. We conclude that the success of the irradiated vaccine depends not only on the generation of a population of antigen-specific T-helper cells in the SLN, but also recruitment of these cells to the lungs before challenge.

Animals↗

PubMed1992

Evaluation of metaiodobenzylguanidine heart and lung extraction fraction by first-pass analysis in pigs.

Metaiodobenzylguanidine (MIBG) is a norepinephrine analog that can be used to study cardiac sympathetic innervation. Most of the kinetic data on MIBG, however, have been obtained in vitro from adrenal chromaffin cells. To elucidate MIBG cardiac kinetics in vivo, we measured the first-pass extraction fraction (EF) of MIBG in pig heart and lungs and determined the relationship between the cardiac EF and myocardial blood flow (MBF) before and after dipyridamole, cocaine and imipramine. The first-pass lung EF was 24% +/- 0.80% (mean +/- s.e.). The baseline cardiac EF of MIBG was 79% +/- 1.6%. With dipyridamole, MBF increase significantly and the EF fell (82% +/- 2.5% to 71% +/- 3.5% baseline compared to 0.03 mg/kg/min dipyridamole, p less than 0.001), indicating that the cardiac EF of MIBG is dependent on MBF. Cocaine infusion had no effect on MBF or EF. Imipramine caused a significant increase in the EF (72% +/- 3.5% versus 77% +/- 2.5%, baseline versus imipramine p = 0.032) without a change in MBF. In adrenal chromaffin cells, cocaine and imipramine decrease MIBG uptake, suggesting that adrenal chromaffin cells may be an inappropriate model for studying MIBG kinetics in cardiac sympathetic neurons.

3-Iodobenzylguanidine↗

PubMed1991

Lung cancer in patients younger than 40 years of age.

The records of 52 patients younger than 40 years of age who had bronchogenic carcinoma diagnosed between 1965 and 1985 were reviewed. The preponderance of adenocarcinoma (54%), the lower male-female ratio in this age group compared with patients age 40 or older (2:1), the importance of cigarette smoking as a causative factor (80% of patients), the long mean duration of symptoms (5 months), and the high incidence of advanced stage at diagnosis (77% Stages III and IV) in these patients are findings similar to those reported in other published series. There was no significant difference in resectability (23% versus 19%), median survival length (5.3 months versus 6.9 months), median survival length of patients who had surgical resection (10.5 months versus 10.8 months), and 5-year survival rate (11.5% versus 6.3%) in these patients compared with a randomly selected group of 260 patients with lung cancer who were age 40 or older.

Adenocarcinoma↗

PubMed1991

Numbers and percent of T lymphocytes in bovine peripheral blood during the periparturient period.

To determine if periparturient immunosuppression in dairy cattle might be due to an alteration in total numbers of percent of T lymphocytes, we examined the numbers and percent of T lymphocyte subsets in peripheral blood from periparturient dairy cows, some of which received recombinant bovine granulocyte colony stimulating factor (rbG-CSF) during the study. Beginning 2 weeks preparatum through 4 weeks postpartum, peripheral blood mononuclear cells (PBMC) were collected and labeled with monoclonal antibodies to BoCD5, BoCD4, and BoCD8, and the percent of cells positive for each marker measured by flow cytometry. The percent of PBMC expressing BoCD5 (total T cells), and BoCD8 (T suppressor/cytotoxic cells) was not significantly different between the groups, or at different times before and after calving. The percent of PBMC expressing BoCD4 (T helper cells) was not significantly different between the groups, however, within both groups there was a higher percent of BoCD4+ cells after calving than during the prepartum period. In cows receiving rbG-CSF, total numbers of PBMC were significantly increased compared to controls during the postpartum treatment period.

Animals↗

PubMed1991

Ribose infusion accelerates thallium redistribution with early imaging compared with late 24-hour imaging without ribose.

To determine if early (4-h) thallium-201 imaging with ribose infusion would enhance detection of thallium redistribution better than late (24-h) imaging without ribose infusion, 15 patients with coronary artery disease underwent thallium stress tests by both methods within 2 weeks. All 15 patients had quantitative coronary angiography. After immediate postexercise planar imaging during the first of two exercise tests, patients were randomized to receive either intravenous ribose (3.3 mg/kg per min) or a control infusion of saline solution for 30 min. Images performed at 4 h for the ribose study were compared with those at 24 h for the saline control study. During the second test, exercise was carried to the same rate-pressure product and each patient received the opposite infusion. Four-hour postexercise images after ribose infusion identified 21 reversible defects not seen in the 24-h saline study. Three reversible defects were seen only in saline studies, but not with ribose at 4 h (p less than 0.01); 15 reversible defects were seen with both tests. When analyzed with respect to the 31 vascular territories supplied by a coronary artery with a greater than 50% stenosis, 8 territories had reversible defects present in the ribose but not the saline study and the saline study did not demonstrate reversible defects in territories that were seen in the ribose study (p less than 0.01). In 14 of these territories, reversible defects were seen with both tests. In 6 of 15 patients, additional vascular territories with reversible defects were identified after ribose infusion. It is concluded that ribose enhances the detection of thallium redistribution at 4 h compared with 24-h control images in patients with coronary artery disease and, therefore, substantially improves the identification of viable ischemic myocardium.

Aged↗