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Biomedical subjects

C M Turner

Publications and source records attributed to C M Turner.

At least 37 records · Page 2Linked to original sources
PubMed2000

Attitudinal effects of degrading themes and sexual explicitness in video materials.

This study examined the independent and interactive effects of sexual explicitness and degrading themes toward women on mens' attitudes following exposure to video presentations of male-female interactions. Subjects were 83 male college students who viewed video vignettes under one of four stimulus conditions: (a) sexually explicit/degrading, (b) sexually explicit/nondegrading, (c) nonexplicit/degrading, and (d) nonexplicit/nondegrading. Results revealed that men exposed to degrading material, regardless of explicitness, were significantly more likely to express attitudes supportive of rape, while explicitness had no significant main or interactive effect on these attitudes. Further, the interaction of explicitness with degradation was found to impact scores on a measure of sexual callousness. Theoretical and clinical implications of these findings are discussed.

Adult↗
PubMed1999

Analysis of ploidy (in megabase chromosomes) in Trypanosoma brucei after genetic exchange.

The megabase chromosomes of Trypanosoma brucei are normally diploid, but the extent to which this ploidy is maintained when parasites undergo genetic exchange is not known. To investigate this issue, a panel of 30 recombinant clones resulting from the co-transmission through tsetse flies of three different parental T. brucei lines in all pair-wise combinations (STIB 247, STIB 386 and TREU 927/4) were examined. These clones are products of 28 different mating events; four of them result from self-fertilisation and the others are F1 hybrids. DNA contents of the three parental lines were determined by flow cytometry and shown to differ only slightly with DNA content increasing in the order 927/4 < 247 < 386. Flow cytometry of the recombinant clones indicated DNA contents were similar to the parents in 28 clones and raised approximately 1.5 times the parental values in only two. The two F1 hybrid progeny with raised DNA contents were shown by marker analysis to be trisomic for seven independent loci indicating that they were probably triploid whereas progeny with DNA contents similar to parental values inherited a single allele from each parent for four independent loci indicating that they were diploid.

Animals↗
PubMed1999

A high level of mixed Trypanosoma brucei infections in tsetse flies detected by three hypervariable minisatellites.

The issue of whether genetic exchange occurs at a significant frequency in natural populations of Trypanosoma brucei is controversial and one of the arguments against a high frequency has been the apparent lack of host infections with mixtures of trypanosome genotypes. Three minisatellite markers (MS42, CRAM, 292) within the coding regions of three genes have been identified and PCR based methods developed for detecting variation at these loci using crude lysates of infected blood as templates. Initial PCR analysis, using primers flanking the repeats, of DNA from two cloned stocks of the parasite has shown that two DNA fragments of different size were amplified from each stock. Analysis of the inheritance of these fragments into the F1 progeny of crosses demonstrated that the different size fragments were alleles that segregated in a Mendelian manner. The alleles at each of the three loci segregated independently consistent with their localisation on three different chromosomes. Analysis of a series of cloned isolates from tsetse flies showed that these loci were highly variable giving heterozygosities of 94% and the identification of 12 distinct alleles in a sample of 17 cloned isolates. In order to determine whether isolates are heterogeneous in terms of trypanosome genotype, the allelic variation at these three loci was examined in uncloned samples from tsetse flies isolated in Kiboko, Kenya and Lugala, Uganda. A significant proportion of the isolates (36% in Lugala and 47% in Kiboko) contained more than two alleles at one or more of the loci thus demonstrating that a high proportion of tsetse flies were infected with more than one genotype of trypanosomes. This was established, unequivocally, for two isolates by generating a series of cloned trypanosome lines from each and determining the genotype of each clone; one isolate (927) contained seven different genotypes with a high proportion of the possible combinations of alleles at each locus. These results indicate the possibility of frequent genetic exchange in the field, they imply that a significant proportion of mammalian hosts must contain mixtures of different trypanosome genotypes and they demonstrate the advantages of using minisatellite markers for the analysis of the population structure of T. brucei.

Alleles↗
PubMed1999

T-Cell responses during Trypanosoma brucei infections in mice deficient in inducible nitric oxide synthase.

We have investigated the possibility that nitric oxide (NO) synthesis may affect the course of a trypanosome infection via T-cell responses using mice deficient in inducible NO synthase (iNOS). Parasitemia levels increased at the same rate in both iNOS-deficient homozygous and control heterozygous mice, and peak parasitemia values were the same in both groups. However, the heterozygous mice maintained higher parasitemia levels after the peak of an infection than the homozygous mice due to a decrease in the rate of clearance of parasites. In iNOS-deficient mice there was an increase in the numbers of total CD4(+) cells and activated (interleukin-2 receptor-expressing) CD4(+) cells in infected mice compared with the numbers in uninfected mice. Spleen cells from infected iNOS-deficient mice displayed increased proliferative responses and gamma interferon secretion when stimulated in vitro than those of control mice. These data suggest that NO production depresses T-helper 1-like responses generated during Trypanosoma brucei infections, thus promoting the survival of the parasite.

Animals↗
PubMed1999

Antigenic variation in Trypanosoma brucei infections: an holistic view.

Trypanosoma brucei parasites undergo clonal phenotypic (antigenic) variation to promote their transmission between mammals and tsetse-fly vectors. This process is classically considered to be a mechanism for evading humoral immune responses, but such an explanation cannot account for the high rate of switching between variable antigens or for their hierarchical (i.e. non-random) expression. I suggest that these anomalies can be explained by a new model: that antigenic variation has evolved as a bifunctional, rather than as a unifunctional, strategy that not only evades humoral immune responses but also enables competition between parasite strains in concomitantly infected hosts. This competition causes a depression of cellular responses. My proposal gives rise to a number of testable predictions. First, low numbers of trypanosomes should express some variable antigen types (VATs) in infections several weeks before these VATs are detectable. Second, as an infection progresses, the number of VATs expressed simultaneously in the population should decrease. Third, immunisation to generate a T helper 1 response against those VATs that are expressed most frequently should lower parasitaemias and reduce virulence.

Animals↗
PubMed1998

Distinct roles for the actin and microtubule cytoskeletons in the morphogenesis of epidermal hairs during wing development in Drosophila.

We have found that the actin and microtubule cytoskeletons have overlapping, but distinct roles in the morphogenesis of epidermal hairs during Drosophila wing development. The function of both the actin and microtubule cytoskeletons appears to be required for the growth of wing hairs, as treatment of cultured pupal wings with either cytochalasin D or vinblastine was able to slow prehair extension. At higher doses a complete blockage of hair development was seen. The microtubule cytoskeleton is also required for localizing prehair initiation to the distalmost part of the cell. Disruption of the microtubule cytoskeleton resulted in the development of multiple prehairs along the apical cell periphery. The multiple hair cells were a phenocopy of mutations in the inturned group of tissue polarity genes, which are downstream targets of the frizzled signaling/signal transduction pathway. The actin cytoskeleton also plays a role in maintaining prehair integrity during prehair development as treatment of pupal wings with cytochalasin D, which inhibits actin polymerization, led to branched prehairs. This is a phenocopy of mutations in crinkled, and suggests mutations that cause branched hairs will be in genes that encode products that interact with the actin cytoskeleton.

Actin Cytoskeleton↗
PubMed1998

Chemotherapy accelerates the development of acquired immune responses to Schistosoma haematobium infection.

Treatment of 41 Schistosoma haematobium-infected children, 5-16 years old, with the drug praziquantel induced a switch from a predominantly IgA-specific antibody response to a predominantly IgG1 response within 12 weeks. A cross-sectional survey suggests that the same switch occurs naturally, but over several years, as children age (n = 251). The switch may be driven by alterations in cytokine levels in response to the release of antigens by dead or damaged parasites. Adults are more resistant to schistosome infection than children, and the switch to an "adult" response suggests that praziquantel treatment may have an immunizing effect, with benefits extending beyond a transient reduction in levels of infection.

Adolescent↗
PubMed1997

The rate of antigenic variation in fly-transmitted and syringe-passaged infections of Trypanosoma brucei.

Rates of antigenic variation were measured in vivo in several populations of cloned lines of Trypanosoma brucei before and after cyclical transmission through tsetse flies. Two cloned lines were adapted for use in laboratory conditions by extensive syringe passaging and rates of antigenic switching/cell/generation were less than 3 x 10(-6) and 1 x 10(-4) in each line. Rates of switching were then determined after fly transmission of the first line and generated per capita rate values of greater than 2 x 10(-3) in three of four populations examined. In the fourth population the switch rate was lower: less than 7 x 10(-5) switches/ cell/generation. These data show that rates of antigenic variation are several orders of magnitude lower in syringe-passaged lines, such as those routinely used in the majority of laboratory studies, compared with most recently fly-transmitted lines. They also show that the reduction in switching rate associated with syringe passaging is reversible and is thus unlikely to be caused by mutation.

Animals↗
PubMed1997

Trypanosoma brucei: lack of cross-resistance to melarsoprol in vitro by cymelarsan-resistant parasites.

We have examined cross-resistance between trypanocidal drugs using a well-characterised drug-sensitive line, 247, and its cymelarsan-resistant derivative, 247melCyR. The cymelarsan-resistant line was cross-resistant to trimelarsen and melarsen oxide, and partially cross-resistant to two diamidines, pentamidine and berenil (diminazene aceturate). It was cross-resistant to lipid-soluble melarsoprol in vivo but to only a trivial degree in two in vitro assays. The potential role of adenosine transport in arsenical-induced killing of parasites was investigated. Adenosine, adenine, and the diamidines, but not inosine, were able to inhibit killing of drug-sensitive STIB 247 trypanosomes by cymelarsan and melarsen oxide in a concentration-dependent manner. These results are consistent with the view that these arsenical compounds enter trypanosomes via an adenosine-specific transporter. Melarsoprol-induced killing of trypanosomes was unaffected, however, by either purine and to only a slight degree by the diamidines. These data suggest that melarsoprol can enter trypanosomes by a route other than through an adenosine transporter and that there may be two mechanisms contributing to arsenical resistance in this drug-resistant line of trypanosomes.

Adenine↗
PubMed1996

Inhibition of growth of Trypanosoma brucei parasites in chronic infections.

The growth of Trypanosoma brucei parasites in chronic infections was investigated by superimposing upon chronic infections, secondary infections in which all parasites expressed the same variable antigen type (VAT). The fate of trypanosomes in secondary infections could then be monitored using the VAT as a marker to discriminate cells in primary and secondary infections and thus enable growth to be observed separately from its interactions with antigenic variation on the part of the parasite and specific immune responses of the host. Our results show that as an infection proceeds, the growth rate is progressively inhibited in mice and sheep, suggesting that inhibition is a general feature of chronic infections. Inhibition was not specific to either the stock or the VAT of the trypanosome, but the degree of inhibition did vary between stocks. Inhibition appeared to be mediated by a lowering of the rate of replication of 'slender'-form parasites rather than by an increase in either the rate of differentiation from dividing slender to non-dividing 'stumpy' forms or the mortality caused by non-specific immune mechanisms. Evidence indicated that the development of specific immune responses to non-variant parasite antigens was also unlikely. These data constitute, we believe, the first evidence for negative regulation of growth in vivo, which may be an important determinant of the virulence of trypanosome infections.

Animals↗
PubMed1996

Characterisation of cloned lines of Trypanosoma brucei expressing stable resistance to MelCy and suramin.

Two cloned drug-sensitive stocks of Trypanosoma brucei (STIB 247 and STIB 386) were each used to generate cloned lines expressing resistance to the melaminophenyl arsenical drug cymelarsan (247MelCyR and 386MelCyR) and to suramin (247SurR and 386SurR). The drug-resistance phenotypes were stable after passaging in mice in the absence of drug pressure and three of the lines were transmitted through tsetse flies with no alteration of drug-resistance. There was no evidence of cross-resistance between melCy and suramin in vivo. Twenty-four hour growth inhibition assays were conducted on bloodstream and procyclic forms in axenic in vitro cultures. Suramin-resistance was expressed in bloodstream forms but not in the procyclic stage, while the melCy-resistant lines expressed melCy-resistance in both stages. No cross-resistance between melCy and suramin was observed. Cross-resistance between melCy and another arsenical drug, melB (melarsoprol), was observed in vivo, but to only a very limited extent in vitro. We propose that this difference between the in vivo and in vitro results for melB may indicate that an alteration in a surface adenosine transporter responsible for reduced melCy uptake was bypassed by melB over 24 hours in vitro.

Animals↗
PubMed1995

Trypanosoma brucei: inheritance of kinetoplast DNA maxicircles in a genetic cross and their segregation during vegetative growth.

The inheritance of maxicircle DNA was determined using a polymorphic EcoRI restriction site in the maxicircle variable region. In 11 hybrid progeny from a genetic cross of two stocks of Trypanosoma brucei, 7 progeny apparently inherited maxicircles uniparentally from either parent, in agreement with the results from previous studies, but in 4 progeny inheritance was biparental. Three subclones from 2 of these 4 progeny were made, and in these the maxicircles of only one parental type were detected. These data are considered in terms of a simple model whereby half the maxicircle genomes are inherited from each parent into progeny at meiosis with subsequent stochastic segregation at each mitotic division. This model generates a quantitative prediction as to the period of time required for fixation of inheritance to a uniparental pattern which provides a reasonable fit to the experimental data. These results provide an explanation as to why previous studies have shown that maxicircles are (apparently) inherited uniparentally: the kinetoplast is a unitary organelle inherited faithfully at cell division, but the maxicircles that it contains are best considered as a population that divides stochastically. Consideration of the model also explains why maxicircle populations are homogeneous.

Animals↗
PubMed1995

Morphogenesis of Drosophila pupal wings in vitro.

We have developed an in vitro culture system which supports the differentiation of Drosophila pupal wings. Cultured wings develop marginal bristles and wing veins, and wing cells form a single prehair at their distal vertex at the appropriate developmental stages. We have tested two molecules with well defined activities to determine the usefulness of this system for applying pharmacological approaches to wing differentiation. Cycloheximide (CY) is a small molecule which inhibits protein synthesis. We found that 50 nM CY rapidly blocks all stages of wing differentiation without lowering cell viability. Chitinase is an enzyme which cleaves chitin polymers and is involved in normal cuticle apolysis. Chitinase applied prior to 28 h apf caused a contraction of the wing without affecting the general wing pattern. We have detected connections between the epithelium and pupal cuticle that are presumably targets of chitinase and are necessary for maintaining normal tissue shape during morphogenesis. Later in development exposure to chitinase caused a loss of normal prehair and bristle polarity, and high doses resulted in a severe disruption of the actin cytoskeleton.

Acetylglucosaminidase↗
PubMed1995

Replication, differentiation, growth and the virulence of Trypanosoma brucei infections.

This study had 2 objectives: first, to investigate how the processes of slender form replication, of differentiation from dividing slender to non-dividing stumpy forms, and of stumpy mortality, combine to determine the initial (acute-phase) growth rate of Trypanosoma brucei populations; second, to determine how acute-phase growth rates influence parasite densities during the subsequent, chronic phase of infection. During the acute phase, slender and stumpy populations both grew approximately exponentially, the latter more slowly than the former. Mathematical models showed how this difference in slender and stumpy growth rates can be explained in terms of heterogeneous replication and differentiation rates. Stumpy life-expectancy was determined for one stock and found to be age-dependent with a half-life of 48-72 h, much larger than observed population doubling times of 5-10 h. A comparison of cloned stocks showed that the highest parasite densities during the chronic phase were associated with the highest acute-phase growth rates of both the whole parasite population and of the subpopulation of slender forms. By contrast, high chronic-phase parasitaemias artificially produced following rapid syringe passage were associated with low acute-phase growth rates of slender forms. Syringe-passaging is a laboratory procedure which selects for virulent parasites, but these parasites behave differently from naturally virulent stocks.

Animals↗
PubMed1994

Malaria parasites undergo antigenic variation at high rates in vivo.

The rates of switching between expression of variable antigen types (VATS) have been investigated in vivo in a cloned line of Plasmodium chabaudi chabaudi. VAT-specific hyperimmune sera combined with an immunogold-silver staining technique were used to detect VATS, and five estimates of VAT-specific switching rates were determined for three of them. VAT-specific switching rates were consistent for each VAT and differed between VATS in the range 1.3 x 10(-2) to 4.3 x 10(-4) switches per schizont per generation. This variation suggests that hierarchical expression of VATS in an infection may be determined by switch rates. A minimum estimate of the overall switching rate was determined by summation of the VAT-specific rates in each of two experiments. In both cases the results showed that at least 1 in every 80 schizonts switched VAT expression every generation. This is the first report of antigenic switching rates for malaria parasites measured in vivo in the presence of minimal specific immune pressure, and is the first to show that VAT-specific switching rates vary between VATS. We conclude that switching is rapid and spontaneous, and is regulated, at least in part, by the VATS involved.

Animals↗