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Biomedical subjects

M E Scott

Publications and source records attributed to M E Scott.

At least 19 recordsLinked to original sources
PubMed2006

High transmission rates restore expression of genetically determined susceptibility of mice to nematode infections.

This study investigated why the susceptible or resistance phenotype to the nematode Heligmosomoides polygyrus was lost when susceptible (C57BL/6) and resistant (Balb/c) strains of mice were housed together in indoor arenas with continuous transmission of the parasite larvae present in peat trays (Scott, 1991). First, both strains expressed their normal phenotype when given a controlled challenge while living in arenas, and when experimentally infected with only 5 parasite larvae. To test whether chronic exposure to peat altered the resistance phenotype, mice were given a challenge infection while living on peat. C57BL/6 mice living on peat had higher egg production and higher worm numbers than Balb/c mice, except at 2 months post-challenge. Finally, natural transmission rates were increased in arena experiments through either regular replacement of arena mice with naïve mice or direct introduction of additional larvae. A transient difference in infection levels between strains was detected in response to a modest increase in transmission whereas a 10-fold increase in transmission allowed C57BL/6 mice to exhibit the typical profile of high egg production and elevated worm numbers. These data indicate that C57BL/6 mice are less able to regulate parasite numbers at high transmission rates compared with lower transmission rates.

Analysis of Variance↗
PubMed2006

Performance of beef heifers grazing stockpiled fescue as influenced by supplemental whole cottonseed.

The objectives of this study were to determine the composition of stockpiled fescue from December through February over 2 yr and to determine the performance of heifers grazing stockpiled fescue with or without supplemental whole cottonseed. In early December, 36 heifers (initial BW 277 +/- 0.70 kg, yr 1; 266 +/- 2.2 kg, yr 2; and initial BCS of 5.0 +/- 0.04) were assigned randomly to 6 groups. Each group was assigned randomly to a 2.4-ha tall fescue pasture (98% endophyte infected), which had received 76 kg of N/ha on September 1. Group was the experimental unit for all measures. Forage DM available during grazing (to ground level) averaged 3,913 and 5,370 kg/ha in yr 1 and 2, respectively. The pasture was strip-grazed for 83 d, with daily forage allocation. Three groups were fed whole cottonseed (0.90 kg of DM/heifer; 24.4% CP, DM basis) daily at 0.33% of BW, and a small amount of a corn-based concentrate (0.19 kg of DM/heifer) to assure complete cottonseed consumption. Nutritive value of forage (dry basis) was determined each week by sampling each pasture to the 5-cm target grazing height. Forage disappearance was estimated every 2 wk from pre- and postgraze forage mass. Forage CP was 16.8% in yr 1 and 12.6% in yr 2. In vitro true organic matter digestibility (IVTOMD) was 82.0 and 71.9%, and ADF was 25.9 and 30.7% in yr 1 and 2, respectively. Most indicators of forage quality declined slightly through the winter, although they recovered in late winter in yr 1. The proportion of fescue that was green declined (P < 0.05) from December (79% in yr 1 and 64% in yr 2) to February (62% in yr 1 and 52% in yr 2). Green tissue averaged 20.4 and 15.2% CP, 91 and 87% IVTOMD, and 22.1 and 23.3% ADF in yr 1 and 2, respectively. Brown tissue averaged 10.3 and 8.5% CP, 64 and 62% IVTOMD, and 35.7 and 37.4% ADF in yr 1 and 2, respectively. Shrunk ADG (0.46 vs. 0.56 kg/d in yr 1 and 0.23 vs. 46 kg/d in yr 2) and change in BCS (- 0.03 vs. 0.33 in yr 1 and 0.13 vs. 0.5 in yr 2) was greater (P < 0.05) for supplemented heifers. Supplemented heifers had greater serum urea nitrogen in yr 1 (9.5 vs. 10.5 mg/dL; P < 0.07) and yr 2 (7.2 vs. 8.6 mg/dL; P < 0.01). Forage disappearance was similar between supplemented and unsupplemented heifers (3.19 vs. 3.39 kg.heifer(-1).d(-1) in yr 1 and 4.14 vs. 4.17 kg.heifer(-1).d(-1) in yr 2, respectively). Heifers responded to supplementation, but performance was lower than expected based on forage nutrient content.

Animal Feed↗
PubMed2004

Microsatellite analysis reveals that female mice are indiscriminate when choosing infected or dominant males in an arena setting.

Considering that both infection and dominance status can be conveyed through urinary odours and both are thought to affect mate choice, the present study assessed the role of infection and male dominance status on female mate choice in arena enclosures. Three male CD-1 mice were simultaneously introduced into each of 4 spatially complex arenas (3.0 x 0.6 x 0.4 m high) for 24 h prior to introduction of 5 females into each arena. During the first mating sequence (i.e. Mating 1), all 3 males were uninfected. Prior to Mating 2, the dominant male in each arena was infected with 200 L3 of Heligmosomoides polygyrus (Nematoda). Prior to Mating 3, the dominant male was drug-treated to remove the parasite. Dominance was assessed by the absence of rump or tail wounds (Freeland, 1981). Females were removed from the arena when visibly pregnant, and returned for subsequent mating 2 weeks following parturition. Paternity was determined by microsatellite analysis of each pup. Multi-male mating (i.e. mating with 2 or all 3 males) was a common strategy among females as littermates were sired by 2 or all 3 males in 64 % of the litters. Contrary to expectation, the dominant male did not sire the majority of offspring in any of the mating sequences, and infection and subsequent drug treatment of the dominant male did not have a significant impact on female mate choice. In addition to methodological differences in paternity determination (i.e. DNA analysis versus behavioural observations and/or phenotypic traits), these findings may be further explained by the spatial complexity of the experimental arenas.

Animals↗
PubMed2003

Susceptibility to IVM in a field strain of Haemonchus contortus subjected to four treatments in a closed sheep-goat flock in Kenya.

Susceptibility to IVM (IVM) of "strain A" Haemonchus contortus which had been exposed to IVM four times over a 2-year period was compared to IVM susceptibility of "strain C" H. contortus which had no prior field exposure to IVM, by in vivo and in vitro methods. In vivo, the percentage reduction in faecal egg counts (FEC) and the total worm counts (TWC) were compared between control animals (lambs and kids) and animals treated with low dose IVM (20 microg/kg). In vitro susceptibility to IVM was evaluated by larval migration inhibition (LMI) after the two strains of H. contortus were exposed to different concentrations of IVM. The dose response, measured as the proportion of larvae inhibited from migrating, was used to estimate LD(50). Although differences in response to IVM in the in vivo determinations were not significant, "strain A" H. contortus had a significantly higher LD(50) than "strain C" in the LMI assay. Coincident with the conduct of the in vivo experiment, it was observed that "strain A" H. contortus established and survived better than "strain C" in the control lambs.

Animals↗
PubMed2002

Dietary pectin, but not cellulose, influences Heligmosomoides polygyrus (Nematoda) reproduction and intestinal morphology in the mouse.

Dietary texture has been reported to influence parasite establishment and survival, but to what degree this relationship is modified by either the type or quantity of dietary fibre is unknown. Using a 2 x 4 factorial design, we explored the relationship between fibre type (soluble pectin vs insoluble = cellulose) and fibre quantity (0, 5, 10 and 20% by dry weight) on parasitic outcomes in BALB/c mice infected with 100 Heligmosomoides polygyrus (Nematoda) larvae. Pectin, but not cellulose, exerted a significant effect on parasite egg production. Following in vitro culture of female worms, increasing levels of dietary pectin were associated with increasing release of eggs. Yet this pattern was not observed in vivo, where per capita egg production peaked at the 10% pectin concentration, but was very low in mice fed 20% pectin. Parasite establishment was elevated in mice fed 20% pectin, but was unaffected by cellulose concentration. Neither type nor quantity of fibre affected H. polygyrus survival or spatial distribution along the gastrointestinal tract. To what degree differences in parasite establishment and reproduction could be attributed to the marked effects of pectin on gut morphology (increased intestinal length, villus length, mucosa thickness and villus/crypt ratio) requires further exploration. Our data indicate that cellulose is preferable to pectin as the source of fibre for experimental diets as cellulose did not affect H. polygyrus establishment, reproduction or survival during a 4-week primary infection.

Animals↗
PubMed2002

Female mice mate preferentially with non-parasitized males.

If parasitic infection is a driving force in female mate choice, then females should preferentially select parasite-free males. The role of infection on female mate choice in mammals was assessed using a 3-chambered apparatus. A female CD-1 mouse was allowed to choose between 2 tethered male mice, 1 uninfected and 1 infected with 200 larvae (L3) of the intestinal nematode Heligmosomoides polygyrus. Both uninfected and infected males were equally receptive to the oestrous females, and females did not differ in the number of visits and time spent exploring the 2 males. Female time preference was not a useful predictor of ultimate mate choice, whereas first mount preference of the female was a reliable indicator. Results indicate that female mice preferentially mated with uninfected males as evidenced by first ejaculation choice, but that male infection status did not significantly affect female reproductive success. Interestingly, litters sired by infected males contained a significantly higher percentage of females suggesting that parasite-induced hormonal changes may alter the sex ratio of the offspring. This study provides the first direct evidence of the impact of parasitic infection on mammalian mate choice.

Animals↗
PubMed2002

Standardised monitoring of patients on long-term medication in primary care.

A three-year pilot study was initiated in collaboration with three general practices to develop a standardised monitoting (SM) system to ensure that chronically sick patients on long-term medication, such as thyroxine, diuretics angiotensin convening enzyme (ACE) inhibitors statins and antirheumatics were reliabily monitored following fixed protocols. A high standard of care was achieved, which included identifying and following up patients with borderline or unacceptable results and persistent non-attendees. In addition, the scheme guaranteed that a current set of results was provided in time for clinical review.

Chronic Disease↗
PubMed2001

Directed polar secretion of protease from single cells of Vibrio cholerae via the type II secretion pathway.

Bacteria have long been thought of as little more than sacks of homogeneously distributed enzymes. However, recent cytological studies indicate that bacteria are compartmentalized with proteins involved in processes such as cell division, motility, chemotaxis, and development located at distinct sites. We have used the green fluorescent protein as a reporter to determine the cellular distribution of the extracellular protein secretion (eps)-encoded type II secretion complex responsible for extracellular secretion of cholera toxin and hemagglutinin/protease in Vibrio cholerae. Real-time monitoring of green fluorescent protein fused to EpsM in living cells indicated that, like the single polar flagellum, the Eps complex is located at the old pole after cell division. Eps-dependent protease secretion was also visualized in single cells by fluorescence microscopy by using intramolecularly quenched casein. This analysis demonstrated that active protease secretion is focused at the poles and colocalizes with the site of the polar Eps apparatus. These results suggest that the type II secretion complex is responsible for directed delivery of virulence factors during cholera pathogenesis.

Bacterial Proteins↗
PubMed2001

Gastrointestinal nematodes, nutrition and immunity: breaking the negative spiral.

Nutritionists have long understood that intestinal nematode parasites have deleterious effects on host nutritional status, but only recently has the importance of malnutrition as a predisposing factor to intestinal nematodes been recognized. Here we review experimental and field studies on the effects of protein, energy, zinc, vitamin A, and iron deficiencies on gastrointestinal (GI) nematodes of humans, livestock, and laboratory rodents, and draw certain conclusions about the state of our current understanding. In general, malnutrition promotes the establishment, survival, and fecundity of these parasites, but the magnitude of the effect depends on factors such as host species, parasite species, particular infection protocol used, magnitude of the infection, severity of the nutritional deficiency, and presence of single or multiple infections and single or multiple nutritional deficiencies. We highlight the Th2 arm of the immune system as a component of primary importance in the association between malnutrition and GI nematode infections. We summarize what is known about underlying mechanisms that may account for the observed patterns. Finally, we suggest future research directions.

Animals↗
PubMed2000

Suppressed T helper 2 immunity and prolonged survival of a nematode parasite in protein-malnourished mice.

Protein malnutrition may increase susceptibility to gastrointestinal parasitic infections, possibly as a result of impaired intestinal and/or systemic T helper 2 (Th2) effector responses induced by down-regulation of Th2 cytokines and/or up-regulation of Th1 cytokines. To test this hypothesis, female BALB/c mice (n = 18/diet) were fed a control (24%), marginal (7%), or deficient (3%) protein diet and given a challenge infection with Heligmosomoides polygyrus. The 3% mice had higher worm burdens at 1, 2, and 4 weeks postchallenge infection (pci), lower increases in serum IgE, reduced intestinal eosinophilia, and depressed mucosal mast cell proliferation and activation at 1-2 weeks pci. To determine whether these suppressed effector responses resulted from altered spleen and mesenteric lymph node (MLN) cytokine production, cells were restimulated in vitro with parasite antigen and cytokine concentrations were measured. Deficient MLN cells secreted significantly less IL-4 and more IFN-gamma at 1-2 weeks pci than did control MLN cells. Deficient spleen cells also secreted more IFN-gamma at 2 weeks pci compared with control spleen cells. From reverse transcription-PCR analyses, the 3% mice also had lower IL-4 mRNA level in spleen and MLN at 1-2 weeks pci. Our study supports the hypothesis that protein malnutrition increases the survival of a nematode parasite by decreasing gut-associated IL-4 (Th2) and increasing IFN-gamma (Th1) within 2 weeks pci, leading to reduced intestinal and systemic Th2 effector responses.

Animals↗
PubMed2000

Zinc deficiency impairs immune responses against parasitic nematode infections at intestinal and systemic sites.

Research on the complex interactions among host nutritional status, parasitic infection and immune responsiveness has focused on the detrimental consequences of parasitic infections on host nutritional status and on mechanisms by which malnutrition impairs immunocompetence. Curiously, relatively few studies have examined the effects of malnutrition on the immune response in the parasite-infected host, and even fewer have considered the events occurring at the intestinal level, where absorption of nutrients occurs, intestinal parasites reside, and the gastrointestinal-associated lymphoid tissues play a role in directing both the local and the more systemic immune responses. Our work using a zinc-deficient nematode-infected mouse model reveals that parasites are better able to survive in the zinc-deficient hosts than in well-nourished hosts; that the production of interleukin-4 in the spleen of zinc-deficient mice is depressed, leading to depressed levels of IgE, IgG(1) and eosinophils; and that the function of T cells and antigen-presenting cells is impaired by zinc deficiency as well as by energy restriction. Given the paramount role of the gastrointestinal-associated lymphoid tissues in inducing and regulating immune responses to intestinal parasites and in orchestrating responses in the spleen and peripheral circulation, we conclude that zinc deficiency (in association with energy restriction) exerts profound effects on the gut mucosal immune system, leading to changes in systemically disseminated immune responses and, importantly, to prolonged parasite survival.

Animals↗
PubMed1999

Energy deficits suppress both systemic and gut immunity during infection.

Protein-energy malnutrition and gastrointestinal nematode infections widely coexist in developing countries. Evidence is provided demonstrating the profound impact of dietary energy deficiency on immune function. Energy-restricted (ER) mice infected with a gastrointestinal nematode showed impaired lymphocyte proliferation and reduced production of Th2 cytokines and lower levels of IgE, parasite-specific IgG1, and eosinophils, which led to higher worm burdens and fecundity. We conclude that mild ER, without concurrent protein malnutrition, can modulate protective immunity from (a) activation early during a primary infection to (b) the expression of acquired immunity during reinfection in both systemic and gut-associated lymphoid tissues.

Animals↗
PubMed1999

Diet texture modifies outcome of a primary infection with Heligmosomoides polygyrus (nematoda) in mice.

To determine if dietary texture altered the establishment, survival and reproduction of Heligmosomoides polygyrus during a primary infection, commercial mouse chow (Purina Chow) was fed in either pelleted or powdered form to 2 groups of infected BALB/c mice, and a semipurified, biotin-fortified, egg-white-based diet was provided in powdered form to a third group of mice. Diet texture (powdered vs. pelleted) modified parasite establishment, as evidenced by higher worm recovery 6 days postinfection (PI) in both groups of mice fed powdered diets compared with the group fed the pelleted diet, but diet texture had no detectable effect on net or per capita egg production or on day 30 worm survival. However, almost twice as many worms were recovered from mice fed the semipurified, powdered diet than those fed either textural formulation of the commercial mouse chow on day 30 PI, indicating that a dietary component in the semipurified diet, such as the single fiber source cellulose, facilitated parasite survival, or that other ingredients in the commercial mouse chow, perhaps the more complex fiber components, reduced worm survival, or both. We conclude that dietary texture influences parasite establishment and that specific fibers that change texture can individually and independently modify H. polygyrus survival.

Animal Feed↗
PubMed1998

The use of fluoro- and deoxy-substrate analogs to examine binding specificity and catalysis in the enzymes of the sorbitol pathway.

The carbohydrate specificity of the two enzymes that catalyze the metabolic interconversions in the sorbitol pathway, aldose reductase and sorbitol dehydrogenase, has been examined through the use of fluoro- and deoxy-substrate analogs. Hydrogen bonding has been shown to be the primary mode of interaction by which these enzymes specifically recognize and bind their respective polyol substrates. Aldose reductase has broad substrate specificity, and all of the fluoro- and deoxysugars that were examined are substrates for this enzyme. Unexpectedly, both 3-fluoro- and 4-fluoro-D-glucose were found to be better substrates, with significantly lower K(m) and higher Kcat/K(m) values than those of D-glucose. A more discriminating pattern of substrate specificity is observed for sorbitol dehydrogenase. Neither the 2-fluoro nor the 2-deoxy analogs of D-glucitol were found to be substrates or inhibitors, suggesting that the 2-hydroxyl group of sorbitol is a hydrogen bond donor. The 4-fluoro and 4-deoxy analogs are poorer substrates than sorbitol, also implying a binding role for this hydroxyl group. In contrast, both 6-fluoro- and 6-deoxy-D-glucitol are very good substrates for sorbitol dehydrogenase, indicating that the primary hydroxyl group at this position is not involved in substrate recognition by this enzyme.

Aldehyde Reductase↗
PubMed1998

Hypobiosis of Haemonchus contortus in natural infections of sheep and goats in a semi-arid area of Kenya.

A total of 42 lambs, 42 kids, 21 ewes and 21 does were necropsied during an investigation of the epidemiology of Haemonchus contortus infection of sheep (Red Maasai) and goats (Small East African Goat) in a semi-arid area of Kenya. Availability and establishment of the infective stages were monitored by the necropsy of 21 tracer lambs and 21 tracer kids. Prevalence of H. contortus was over 90% in both sheep and goats and this species contributed to about 80% of the total worm burden. Only about 10% of the hypobiotic larvae were recovered from the mucosal digest whereas about 90% were recovered from the abomasal contents and washings, thereby suggesting that hypobiotic larvae may be loosely attached to the abomasal mucosa from which they may be dislodged during the processing of the abomasa for examination. Throughout the study, both adult worms and hypobiotic larvae were found in proportions that varied with seasons. Statistically, a higher proportion of hypobiotic larvae was found during the dry months than during the wet months, an indication that hypobiosis was an important feature in the survival of H. contortus during the dry months. Negligible worm burdens were acquired by the tracers during the short rains, suggesting that few H. contortus larvae survived on pasture in this season. The effectiveness of strategic control using ivermectin varied according to the timing in relation to the wet season. Treatment did not influence the seasonal pattern of hypobiosis but the treatment administered before the onset of the rains significantly reduced the numbers of both hypobiotic larvae and the adult worms. Treatment during the rains conferred a temporary relief of adult worm burden but had no impact on hypobiotic larvae.

Animals↗
PubMed1998

Dietary protein and zinc restrictions independently modify a Heligmosomoides polygyrus (Nematoda) infection in mice.

The effects of dietary protein and zinc restrictions on Heligmosomoides polygyrus were compared following primary and challenge infection in female BALB/c mice fed either control (24%), marginal (7%) or low (3%) protein combined with either high or low zinc (60 or 3 mg Zn/kg diet). Dietary protein restriction (3%) resulted in significantly lower body weight gain. As well, blood urea nitrogen (BUN) significantly decreased with decreasing dietary protein level. However, neither plasma albumin concentration nor relative thymus or spleen weights were reduced. Marginal zinc deficiency was confirmed by significantly lower tibia and liver zinc concentration, but food intake, body weight gain, relative thymus and spleen weights, and alkaline phosphatase activity were not altered. On day 29 post-primary infection, worm burdens were significantly higher in mice fed either marginal or low protein and in mice fed a low zinc diet, while parasite egg output was significantly higher in mice fed both low protein and low zinc diet. Immune status was compromised in mice fed low protein (significantly lower serum IgG1 and lower eosinophilia), and in mice fed low zinc diet (significantly lower eosinophilia). Early in the infection, IgE titres were elevated in mice fed low protein or low zinc, but IgE titres declined to levels lower that the control diet groups after 14-21 days. On day 29 post-challenge infection, worm burdens and parasite egg output were significantly higher in mice fed low protein, whereas the other group had expelled almost all parasites. Dietary restriction had no effect on IgE. Significantly reduced serum IgG1 titres and eosinophilia in mice fed 3% protein supported the view that low dietary protein but not low zinc increased host susceptibility to H. polygyrus by compromising host immune function following reinfection in immunized mice.

Animals↗
PubMed1998

Play and therapeutic action. Multiple perspectives.

Children's play that goes unanalyzed within a psychoanalysis, yet leads to therapeutic change, is contrasted with interpreted play that leads to conscious insight. The therapeutic and development facilitating effects of unanalyzed play suggest that substantial analytic work goes on unconsciously. Technical issues arise, therefore, if play is conceptualized as a therapeutic force in its own right. Developmental considerations and inhibitions in play become greater considerations in analytic technique. Two clinical vignettes from the analyses of latency-age girl and boy are presented to illustrate unanalyzed play as an agent in development and mastery of anxieties.

Awareness↗