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Biomedical subjects

W D Smith

Publications and source records attributed to W D Smith.

At least 73 records · Page 4Linked to original sources
PubMed1995

Haemopoietic cell responses in the blood and bone marrow of sheep infected with the abomasal nematode Telodorsagia circumcincta.

The generation of bone marrow and blood haemopoietic progenitor colony-forming cells (CFCs) in sheep given primary or challenge infections with the nematode parasite Telodorsagia circumcincta is described. Ten days after a primary infection, the frequency of early multipotential-CFCs, eosinophil-CFCs, macrophage-CFCs and mast cell or basophil-CFCs was greater than in controls. These frequencies then declined to pre-infection levels by day 21. Blood CFCs (mainly macrophage-CFCs and eosinophil-CFCs) also increased after infection, indicating a migration of CFCs, presumably to the site of infection. Ten days after challenge infection there was less marked myelopoiesis than in the primary infection on day 10, though both eosinophil-CFCs and mast cell or basophil-CFCs were significantly above control values. Blood CFC output (mainly macrophage-CFCs and eosinophil-CFCs) reached a peak 2-6 days after challenge, evidence of rapid recruitment to the site of infection. Telodorsagia circumcincta infection is therefore associated with an increase in myelopoiesis, particularly for the cell types characteristic of the local inflammatory response to abomasal nematodes. There was no correlation between any of the haemopoietic cell responses measured and worm burdens in individual animals after either primary or challenge infection.

Animals↗
PubMed1994

Ingestion of host immunoglobulin by three non-blood-feeding nematode parasites of ruminants.

Host immunoglobulin was detected in homogenates of adult worms or fourth stage larvae of Haemonchus contortus, Ostertagia ostertagi, O circumcincta and Dictyocaulus viviparus, but not in preparasitic third stage larvae of H contortus. All the worms had been washed in detergent before being homogenised to remove any immunoglobulin adhering to the cuticle. This procedure, the concentrations of immunoglobulin detected and observations on sections of the worms stained with fluorescent anti-sheep immunoglobulin, all suggested that the immunoglobulin had been ingested, even by the non-blood-feeding species. This finding suggests that the Ostertagia species and D viviparus may be susceptible to vaccination by the gut antigen approach, a method with considerable promise for blood-feeding parasites like H contortus and Boophilus microplus.

Animals↗
PubMed1994

Protection studies with integral membrane fractions of Haemonchus contortus.

Techniques for targetting glycoproteins integral to the luminal membrane of the intestinal cells of Haemonchus contortus were used to isolate fractions of whole parasites with protective antigen potential. Sheep immunization trials with various candidate fractions revealed one which selectively bound to lectins with specificity for N-acetylgalactosamine and which reduced mean challenge worm burdens by up to 72% and mean faecal egg counts by up to 93%. The luminal surface of the intestines of the Haemonchus recovered from sheep immunized with this antigen were coated with host immunoglobulin, suggesting that the protective effect was due to antibodies interfering with the function of the gut. Further biochemical characterization of this fraction, which has been termed Haemonchus galactose-containing glycoprotein complex (H-gal-GP complex), showed that it could be distinguished from previously described protective antigens of this parasite and that it was only detectable in detergent extracts of the worms.

Acetylgalactosamine↗
PubMed1994

Local eosinophil- and mast cell-related responses in abomasal nematode infections of lambs.

Eosinophil numbers in peripheral blood and eosinophil potentiating activity (EPA) and sheep mast cell protease (SMCP) in efferent gastric lymph were monitored in lambs during infections with Ostertagia circumcincta. Worm burdens, eosinophil numbers in bone marrow, abomasal mucosa and gastric lymph node, as well as mast cell numbers and SMCP concentrations in mucosa and mucus, were determined in post mortem samples. In naive lambs, high and relatively uniform worm burdens were present 10 days after primary infection and these were associated with only mild blood and tissue eosinophilia. By day 21 worm burdens were markedly lower and more variable. There was more evidence of eosinophil and mast cell accumulation in mucosa, and numbers in bone marrow were also higher than on day 10. However, neither EPA nor SMCP were detectable in lymph. By contrast, EPA and SMCP were present in substantial amounts in draining lymph within 48 h of challenge (secondary) infection of previously exposed lambs. EPA was inversely related to worm burdens recovered on day 10, as were abomasal mucosal and mucus SMCP concentrations. Elevated eosinophil numbers were also consistently detected in blood, bone marrow, mucosa and gastric lymph node. The results suggest that host immune defence against secondary, but not primary, exposure to O. circumcincta involves a rapidly mobilised local inflammatory component.

Abomasum↗
PubMed1993

Protection in lambs immunised with Haemonchus contortus gut membrane proteins.

Substantial protection against Haemonchus contortus was induced in lambs by hyperimmunising them with an integral membrane extract of intestines dissected from adult worms. The procedure was effective in young growing animals but did not afford any cross protection against either Ostertagia circumcincta or Nematodirus battus. A serum transfer experiment suggested that the effector mechanism was serum antibody which bound to the brush border membrane of the parasites intestinal cells. Sheep which had acquired immunity to H contortus by previous exposure to a trickle infection did not recognise the gut membrane proteins, which suggested that these are normally hidden from the host.

Animals↗
PubMed1993

Evaluation of aspects of the protection afforded to sheep immunised with a gut membrane protein of Haemonchus contortus.

Experiments were undertaken to evaluate the type of protection conferred against Haemonchus contortus by immunising sheep with H11, a 'hidden' integral gut membrane protein isolated from this parasite. A serial kill experiment showed that worms began to be lost from immunised lambs between seven and 14 days after challenge with a single dose of larvae and adult female worms were more susceptible than male worms. Seven-day-old juveniles survived immunisation even though their intestinal cells became coated with sheep antibody. Immunisation was equally effective against both benzimidazole-resistant and susceptible strains of H contortus. When immunised lambs were subjected to a trickle infection, they were largely protected against the anaemia and egg output observed in the challenge controls. Moreover, they grew as fast and as efficiently as uninfected lambs fed on the same high protein diet and acquired a natural immunity during the course of the trickle infection.

Animals↗
PubMed1993

Evaluation of the VMM turbine for spirometry in the applied physiology laboratory.

The volume measurement module turbine (VMM) was evaluated in 51 subjects for spirometry in applied physiology against the Stead-Wells spirometer (SW) and Wright peak flow meter (WM). The volume and flow ranges (VMM) were, FEV1 1.32 to 3.94 L (mean 2.62, confidence interval [CI] 2.46 to 2.78); forced vital capacity (FVC) 1.97 to 5.06 L (mean 3.50, CI 3.29 to 3.71); and peak expiratory flow rate (PEFR) 290 to 624 L.min-1 (mean 434, CI 407 to 461). The mean difference for FEV1 was 0.09 L (CI 0.05 to 0.14), FVC 0.04 L (CI -0.02 to 0.10), and PEFR 18.0 L min-1 (CI 8.7 to 27.3) less than SW or WM. Bias with FEV1 and FVC was not significant, though PEFR demonstrated a significant proportional error. The repeatability coefficients for FEV1 and FVC were 0.18 and 0.20, comparable to the SW; but for PEFR they were greater, 58.4 versus 33.8 L.min-1 by WM. The VMM turbine is accurate and reliable for the measurement of FEV1 and FVC over the ranges studied; however, care should be taken when interpreting PEFR.

Adult↗
PubMed1993

Ventilatory sensitivity to CO2 in hyperoxia and hypoxia in older aged humans.

Findings from studies of the effects of aging on the human respiratory controller are equivocal. This study assessed the ventilatory response to CO2 in hyperoxia and hypoxia in groups of younger (YS) and older (OS) humans. Two protocols were used. In the first, end-tidal PCO2 (PETCO2) was clamped at 1-2 Torr above rest (eucapnia), and, in the second, PETCO2 was clamped at 7-8 torr above resting PETCO2 (moderate hypercapnia). End-tidal PO2 was clamped at 100 Torr throughout except for two 2-min periods at 500 and 50 Torr. The ventilatory responses for each subject at each PO2 were fitted to the linear equation, VE = S(PETCO2 - B), where VE is minute ventilation, S is the response curve slope, and B is the response curve threshold. In eucapnia, there were no differences in hypoxic and hyperoxic VE between YS and OS. In hypercapnia, hypoxic VE was 24% lower in OS [39.93 +/- 2.71 (SE) l/min] than in YS (52.16 +/- 3.17 l/min). In hypoxia, S was significantly lower in OS (3.25 +/- 0.38 l.min-1.Torr-1) than in YS (4.76 +/- 0.37 l.min-1.Torr-1). We conclude that, in older humans, VE is lower in hypoxia during moderate hypercapnia, resulting mainly from a decreased peripheral chemoreflex CO2 sensitivity.

Adult↗
PubMed1992

Physiological responses of young and elderly men to prolonged exercise at critical power.

The critical power (CP) of a muscle group or individual may represent the highest rate of work which can be performed for an extended period. We investigated this concept in young (n = 13, 24.5 years) and elderly (n = 12, 70.7 years) active men by first determining CP and then comparing responses elicited by 24 min of cycle exercise at power outputs (omega) corresponding to CP. Values from the final 2 min of the 24-min ride were expressed relative to maximal values established in a ramp test. CP for the elderly was only 65% that for the young, but on a relative basis, it was significantly higher both in terms of omega (67 vs 62% of omega max) and oxygen consumption (VO2) (91.5 vs 85.2% of maximum oxygen consumption). There were no group differences in relative values for ventilation (VE), heart rate or respiratory exchange ratio (R). During the 24-min ride, VO2 and R achieved a plateau in both groups, while VE, blood lactate and arterial PCO2 continued to change in the young. It was concluded that CP can be determined in active elderly men, but that CP may not represent a true non-fatiguing work rate in either young or elderly men.

Adult↗
PubMed1992

Forced expiratory volume, height, and demispan in Canadian men and women aged 55-86.

In a random cross-sectional study in London, Canada, forced expiratory volume in 1 second (FeV1.0), height, and demispan (fingerweb to central sternal notch) were measured on 182 men and 212 women of mean ages 70.4 (SD 8.5) and 71.3 (8.2). The mean FeV1.0 for men was 2.55 (0.66) l, and for women 1.80 (0.48) l and declined 29 ml.year-1 and 25 ml.year-1, respectively. The mean FeV1.0 standardized for measured height and calculated height for men was 2.54 (0.61) l and 2.55 (0.62) l in men, and 1.80 (0.46) l and 1.79 (0.45) l in women. There was no significant difference between the two methods of standardization, and the relationship of height to demispan in this independent elderly population was constant across age for both men (2.16) and women (2.17). Linear and proportional regression coefficients to predict FeV1.0 from height and demispan have been generated for this random sample aged 55 to 86 years.

Aged↗
PubMed1991

Further observations on the phagocytosis of Candida albicans by hamster and human oocytes.

Pathogenic yeast, Candida albicans, were incubated with hamster and human oocytes for up to 21 hours in order to determine the nature and time course of phagocytosis of these organisms. Aliquotes of the interacting cells were taken at various time intervals for electron microscopic examination. Some specimens had their zona pellucidae enzymatically removed prior to incubation with yeast, and these specimens showed the most extensive interaction and phagocytosis of Candida. The zona pullucida appears to be an effective barrier to yeast, at least over the time span studied. The observations are consistent with the hypothesis of an initial attachment of yeast via a surface component to oocyte microvilli followed by phagocytic uptake into an endosome. There is no compelling evidence of lysosomal degradation of the yeast over the time course of this study; however, the oocytes appear to undergo some degenerative changes at long incubation times.

Animals↗
PubMed1989

Parasite-specific T cell responses of sheep following live infection with the gastric nematode Haemonchus contortus.

Helper T cell lines recognizing antigen in the context of MHC Class II molecules were generated from peripheral blood mononuclear cells (PBMC) of sheep undergoing a primary or secondary infection with the nematode parasite Haemonchus contortus. The lines were used to identify 15-18, 25-29, 70-80 and greater than 100 kD immunodominant parasite larval antigens fractionated by SDS-PAGE under reducing conditions. Non-specific mitogenic activity in the antigen fractions was not detected. During primary infection PBMC did not respond to soluble antigens or those fractionated on SDS-PAGE, whereas T cell lines generated from these PBMC responded well. T cell lines and PBMC derived after a secondary infection responded similarly to fractionated larval antigen. This indicated that (a) the T cell lines had retained their antigen specificities (as represented by autologous PBMC reactivity) in spite of in-vitro cycles of restimulation with whole larval soluble antigen and subsequent expansion in recombinant human IL-2, and (b) proliferation of the antigen-specific PBMC was predominantly due to helper T cells. Variations between individual sheep in response to fractionated larval antigens was also observed. The pattern of helper T cell reactivity to SDS-PAGE larval antigens correlated poorly with B cell reactivity in the same animals by serum antibody Western blot analysis. These results demonstrate that helper T cell epitopes can be mapped in complex parasite antigen preparations in sheep and that this approach will be useful in the identification of parasite protective antigens in helminthiasis where the cellular or humoral nature of protection is not clearly defined.

Animals↗