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Biomedical subjects

M E Scott

Publications and source records attributed to M E Scott.

At least 73 records · Page 4Linked to original sources
PubMed1988

Effect of repeated anthelmintic treatment on ability to detect predisposition of mice to Heligmosomoides polygyrus and Aspiculuris tetraptera (Nematoda) infections.

Several recent studies have demonstrated predisposition of certain humans to heavy gastro-intestinal nematode infections. This finding has been used to support the concept of community control of nematodes based on selective treatment of the few heavily infected individuals in the community. A mouse model has been used in this study to determine whether those individuals found to be 'predisposed' to heavy infection continue to regain heavy nematode infections following repeated anthelmintic treatments. Re-infection was examined over 3 intervals of 8 weeks in 52 mice and individual worm burdens attained following drug-induced expulsion were analysed. In the case of Heligmosomoides polygyrus, parasite numbers obtained after first treatment were only significantly correlated with those obtained after the second treatment. Re-infection levels in mice during the second and third re-infection periods did not correlate with parasite loads at the beginning of the study. In the case of Aspiculuris tetraptera, correlations after each re-infection period remained significant, although the magnitude of the correlation coefficient decreased with successive re-infection intervals. The data suggest that a selective control programme based on repeated screening to identify heavily infected individuals prior to each treatment would reduce the number of H. polygyrus in the host population 17.6% more than a single screening at the beginning of the control programme, and would reduce the number of A. tetraptera by 14% more than a single screening. Re-infection rates for H. polygyrus were shown to decrease with increasing mouse age whereas re-infection rates for A. tetraptera increased with increasing mouse age.

Age Factors↗
PubMed1988

Predisposition of mice to Heligmosomoides polygyrus and Aspiculuris tetraptera (Nematoda).

The purpose of this study was to determine whether predisposition to Heligmosomoides polygyrus and Aspiculuris tetraptera (Nematoda) exists within a naturally infected population of mice. A breeding mouse population was housed in a spacious arena in which endemic infections of H. polygyrus and A. tetraptera were present. H. polygyrus were over-dispersed in the mouse population. Prevalence reached 100% by the age of 3 weeks; intensity of infection increased to a peak in the 10 to 15-week-old mice, and remained high throughout life. A group of 73 mice was treated with pyrantel pamoate, and the expelled worms were counted. Mice were returned to the arena. Daily egg production was monitored 4, 8, 12 and 14 weeks after treatment. Mice were then killed and numbers of H. polygyrus and A. tetraptera were counted. Significant positive correlations were detected between numbers of H. polygyrus at first treatment and at necropsy, indicating the existence of predisposition. Similar results were obtained for A. tetraptera. Correlations improved when data were analysed by age class of mice. Analyses based on egg-count data during reinfection did not support the hypothesis of predisposition, however. A. tetraptera and H. polygyrus burdens were significantly correlated only in 3 to 4-week-old mice at the time of the treatment.

Animals↗
PubMed1988

Ecological studies on Cyathocotyle bushiensis (Digenea) and Sphaeridiotrema globulus (Digenea), possible pathogens of dabbling ducks in southern Québec.

Over the past 20 yr, recurrent late-summer mortality of dabbling ducks in southern Québec has been attributed to the digenean parasite Cyathocotyle bushiensis. This study attempted to determine whether this parasite was still implicated in the epizootics, and examined aspects of the ecology of the parasite in the definitive host. Comparison of prevalence and mean intensity of infection of all species of Digenea between salvaged carcasses and hunter-shot ducks revealed that C. bushiensis and a second digenean Sphaeridiotrema globulus were both significantly more prevalent in salvaged ducks. Mean intensity of infection was consistently higher for S. globulus in the salvaged carcasses than in hunter-shot ducks. These data provide strong circumstantial support for the hypothesis that C. bushiensis continues to contribute to the annual mortality, but also strongly suggest that S. globulus may be involved. Comparison of the relative numbers of each species of duck between the salvaged carcass sample and the hunter-shot sample revealed that blue-winged teal (Anas discors) occurred significantly more frequently in the salvaged carcass sample whereas wood ducks (Aix sponsa) were common in the hunter-shot sample but were never found in the salvaged carcass sample. A comparison of susceptibility to experimental infection with C. bushiensis revealed that mallards (Anas platyrhynchos), black ducks (Anas rubripes), blue-winged teal, pintail (Anas acuta) and lesser scaup (Aythya affinis) had similar susceptibilities but that wood ducks were significantly less susceptible to infection. Experimental infections also showed that age of mallards significantly influenced the number of parasites obtained 7 days postinfection; ducklings were most heavily infected. Significant differences were detected in the gross pathology caused by C. bushiensis among duck species. Data obtained from sentinel ducks placed in the field for 24 hr revealed that transmission of both C. bushiensis and S. globulus occurs at least between mid-May and mid-September and that large, potentially lethal, infections can be acquired in as little as 24 hr. Finally evidence is presented to suggest that ducks acquire resistance to challenge infections of C. bushiensis.

Age Factors↗
PubMed1987

8-Amino-9-substituted guanines: potent purine nucleoside phosphorylase (PNP) inhibitors.

A series of 8-amino-9-substituted guanines was synthesized and their activity evaluated against human purine nucleoside phosphorylase (PNP). All compounds were found to be potent inhibitors of human PNP (IC50s: 0.17-126 microM). They were also selectively cytotoxic to MOLT-4 lymphoblasts in the presence of a nontoxic amount (10 microM) of the PNP substrate, 2'-deoxyguanosine (GdR). The most potent of these analogs, 2,8-diamino-1,9-dihydro-9-(2-thienylmethyl)-6H-purin-6-one (8-amino-9-(2-thienylmethyl)guanine; PD 119,229) has an IC50 of 0.17 microM (Ki = 0.067 microM), significantly more potent than the known standard, 8-aminoguanosine (IC50 = 1.40 microM). Thus it represents the most potent PNP inhibitor known to date when tested without limiting the concentration of inorganic phosphate.

Cell Line↗
PubMed1987

Preliminary report on 8-amino-9-(2-thienylmethyl)guanine (PD 119,229), a novel and potent purine nucleoside phosphorylase inhibitor.

PD 119,229 [8-amino-9-(2-thienylmethyl)guanine] is a novel and potent inhibitor of human erythrocyte purine nucleoside phosphorylase (PNP) with a Ki of 0.067 microM. In a cell line assay using human MOLT-4 (T cell) and MGL-8 (B cell) lymphoblasts, PD 119,229 alone had no effect on the growth of either cell line at the highest concentration tested (100 microM). However, in the presence of a nontoxic concentration of 2'-deoxyguanosine (10 microM), the IC50 values of PD 119,229 for MOLT-4 and MGI-8 40-fold either cell line at the highest concentration tested (100 microM). However, in the presence of a nontoxic concentration of 2'-deoxyguanosine (10 microM), the IC50 values of PD 119,229 for MOLT-4 and MGI-8 were 0.9 and greater than 100 microM, respectively. The inhibition of growth of MOLT-4 was accompanied by a 40-fold increase in dGTP and a two-fold reduction in GTP, while no alteration in nucleotide profile was noted in MGL-8. Both the inhibition of growth of MOLT-4 and the accumulation of dGTP were substantially prevented by coaddition of 2'-deoxycytidine.

Cell Division↗
PubMed1987

Temporal changes in aggregation: a laboratory study.

Changes in the variance to mean ratio and the parameter k of the negative binomial distribution were used to study temporal changes in the degree of aggregation of the monogenean parasite, Gyrodactylus turnbulli in free-running laboratory populations of the guppy, Poecilia reticulata. The parasite undergoes recurrent epidemic cycles in the host population under conditions of regular immigration of uninfected guppies. During the early phase of the epidemic, heterogeneity among fish together with direct reproduction are thought to contribute to the increasing degree of aggregation. During the increasing phase of the epidemic cycle, parasites become increasingly aggregated in the host population, presumably because of the direct reproduction of the parasite on the surface of a single host. As the peak prevalance and abundance are approached, the parasites become less aggregated with lowest clumping occurring during the declining phase of the cycle. This is thought to be a function of density-dependent death of infected hosts, and density-dependent reduction in parasite survival and reproduction on hosts that recover from infection. This study clearly indicates that the variance to mean ratio and the parameter k of the negative binomial distribution do not quantify the same aspect of the frequency distribution. It is suggested that the variance to mean ratio is a better measure when the prevalence and/or mean burden are changing and when the tail of the distribution is of particular interest, and that k may be a preferred parameter when the zero class or the lightly infected hosts are of primary interest.

Animals↗
PubMed1987

Regulation of mouse colony abundance by Heligmosomoides polygyrus.

Despite the ubiquitous presence of parasites, parasitism has not been considered among the list of regulatory factors in animal populations until recently. A detailed long-term study on the impact of the direct life-cycle nematode Heligmosomoides polygyrus on a breeding population of laboratory mice provides a clear example of the ability of helminths to regulate host abundance. In the absence of the parasite, the mouse population equilibrated at a density of 320 mice/m2 as a result of density-dependent effects on recruitment. When the parasite was added and transmission was maintained at high levels, infected mouse populations equilibrated at densities of less than 18 mice/m2. Reduced rates of parasite transmission and elimination of the parasite from the system both resulted in an increase in mouse density. These results have implications for both ecology and parasitology as they demonstrate a potentially important but often ignored component of host populations that may well influence host abundance and community structure.

Animals↗
PubMed1987

Hatching and survival characteristics of Cyathocotyle bushiensis Khan 1962 (Digenea) eggs and miracidia.

Cyathocotyle bushiensis Khan 1962 is a digenean intestinal parasite of ducks that appears to be involved in seasonal mortality of the definitive host. Temperature dependence of egg hatching and miracidial survival at 25 degrees C were experimentally investigated as part of a study on transmission of the larval stages. Maximum percentage of hatching was obtained at a temperature of 25 degrees C, at which the average hatching time was 21.7 days. The average hatching time decreased linearly from 38.9 days to 9.8 days between 18 and 28 degrees C. Eggs exposed to cold (4 degrees C) prior to incubation at 25 degrees C were significantly less successful in hatching than fresh eggs incubated at the same temperature. Their hatching percentage was much reduced and their average hatching time was increased. Similarly, eggs collected in late autumn (as opposed to summer) and incubated at 23 degrees C had significantly lower hatching success and significantly increased average hatching time. At 25 degrees C, the average life-span of the miracidia was 8.8 h. These results are compared with similar data from other digenean species and their significance is discussed in relation to transmission to the first intermediate host in climatic conditions prevalent in endemic areas.

Animals↗
PubMed1986

Inhibitors of human purine nucleoside phosphorylase. Synthesis, purine nucleoside phosphorylase inhibition, and T-cell cytotoxicity of 2,5-diaminothiazolo[5,4-d]pyrimidin-7(6H)-one and 2,5-diaminothiazolo[4,5-d]pyrimidin-7(6H)-one. Two thio isosteres of 8-aminoguanine.

8-Aminoguanine is a potent inhibitor of purine nucleoside phosphorylase (PNP) and also a substrate of PNP. Two thio isosteres of 8-aminoguanine, 2,5-diaminothiazolo[5,4-d]pyrimidin-7(6H)-one (2) and 2,4-diaminothiazolo[4,5-d]pyrimidin-7(6H)-one (3), which cannot be substrates of PNP, were synthesized and evaluated for their inhibitory activity against PNP. They were found to be weak inhibitors of PNP and to be noncytotoxic for MOLT-4 T-cells in culture.

Cell Division↗
PubMed1986

Acute haemodynamic effects of pinacidil in man.

The acute haemodynamic effects of i.v. pinacidil 0.2 mg kg-1 infused over 8 min were studied in 10 normotensive patients undergoing cardiac catheterisation. Mean arterial pressure fell from 94 +/- 3 mmHg (mean +/- s.e. mean) before infusion to 74 +/- 3 mmHg at 10 min after commencing infusion (P less than 0.001) and during this time heart rate increased from 75 +/- 4 to 106 +/- 7 beats min-1 (P less than 0.001). Significant changes were recorded until the end of the observation period (70 min after commencing infusion). Cardiac index increased from 3.2 +/- 0.2 to 4.0 +/- 0.2 l min-1 m-2 (P less than 0.001) and systemic vascular resistance fell from 16 +/- 1 to 10 +/- 1 units (P less than 0.001) at 10 min after commencing infusion. By the end of the observation period, the values had returned to pre-infusion levels. Only small changes in pulmonary haemodynamics were observed. These results indicate that pinacidil acts as a peripheral arteriolar vasodilator, and as such may have a role in the treatment of arterial hypertension and of cardiac failure.

Adult↗
PubMed1986

Long-term population dynamics of pinworms (Syphacia obvelata and Aspiculuris tetraptera) in mice.

The population dynamics of concurrent infections of Syphacia obvelata and Aspiculuris tetraptera (Nematoda) in laboratory mice were investigated under conditions of constant re-exposure over periods of 56 and 115 days. The results indicate that A. tetraptera burdens equilibrate at a higher level than S. obvelata burdens and that both parasites become aggregated in the mouse population. Parasite burdens were higher following short-term (7 day) exposure of uninfected tracer mice to both parasites when compared with parasite burdens attained over long-term exposure, indicating probable development of immunity. A significant positive correlation was detected between numbers of immature S. obvelata and immature A. tetraptera for both experimental and tracer mice.

Animals↗
PubMed1984

The population dynamics of Gyrodactylus bullatarudis (Monogenea) within laboratory populations of the fish host Poecilia reticulata.

Experiments were undertaken to investigate the factors which influence the transmission dynamics of Gyrodactylus bullatarudis within populations of laboratory guppies. The parasites possess a number of biological attributes which are almost unique amongst helminth parasites of vertebrates. These include the ability to reproduce viviparously and directly on the surface of the host, the ability to survive death of the host (for a short period of time) and the ability to transfer between hosts (despite the absence of a specialized transmission stage in the parasite's life-cycle). Long-term laboratory experiments demonstrated the inability of the parasite to persist within populations of the host in the absence of the continual introduction of naive susceptible fish. With regular addition of susceptible fish, the parasite population exhibited recurrent epidemic behaviour. The magnitudes of the epidemics and the time interval between them, were dependent on the rate at which fish were added to the populations. The parasite was over-dispersed in its distribution within the experimental fish populations and was a significant cause of host mortality (in a manner related to parasite burden). The experimental results suggest that acquired resistance to infection is an important factor determining epidemic behaviour.

Animals↗
PubMed1982

Comparative migration, growth and development of Typhlocoelum cucumerinum sisowi in dabbling ducks and Typhlocoelum cucumerinum cucumerinum in diving ducks.

Experimental infections of mallards (Anas platyrhynchos L.) with Typhlocoelum cucumerinum sisowi (Skrjabin, 1913) and of canvasbacks (Aythya valisineria (Wilson)) with Typhlocoelum cucumerinum cucumerinum (Rudolphi, 1809) revealed significant differences in various parameters of the life-cycle in the definitive host. Both T. c. sisowi and T. c. cucumerinum migrate to the trachea via the abdominal cavity, air sacs and lungs, although T. c. cucumerinum migrate more quickly and more synchronously than T. c. sisowi. Typhlocoelum c. sisowi has a shorter expected life-span than T. c. cucumerinum but grows and reaches maturity more quickly than T. c. cucumerinum. Evidence suggests that T. c. cucumerinum has a higher fecundity than T. c. sisowi. These differences in the patterns of migration, growth and development are related not only to differences between the two host species but also to differences intrinsic to the parasites, and serve to provide biological support for considering them as separate sub-species.

Animals↗
PubMed1982

Spontaneous splenic infarction in polysplenia syndrome.

A case of polysplenia with spontaneous infarction of one of the four spleens is presented. The diagnosis was made by computed tomography (CT), which demonstrated the multiple aberrant right sided spleens, with an area of low attenuation representing infarction of one of the spleens. The associated anomalies of prominent azygos and hemiazygos veins secondary to absence of the suprarenal portion of the inferior vena cava were also seen on CT.

Humans↗