Search PubMed⌕ Search

Biomedical subjects

C J Schofield

Publications and source records attributed to C J Schofield.

At least 109 records · Page 6Linked to original sources

Vector population responses to control interventions.

In 1981, Kenyan authorities attempted eradication of tsetse (Glossina pallidipes) from the Lambwe valley, by sequential aerial spraying of endosulfan. Fly populations were reduced by over 99.9% in the main habitats, but recovered to their original levels within one year. In 1986, an Argentine research team attempted local elimination of domestic Triatominae (Triatoma infestans) in an area of Santiago del Estero. House infestation rates were reduced to an apparent zero, but recovered to pre-control levels in two years. In Sri Lanka, a combination of mosquito control with active case detection and treatment reduced malaria incidence to just 17 cases in 1964. Interruption of the programme then saw case incidence return to over 500,000 by 1969. These three examples-from African trypanosomiasis, South American Chagas disease and malaria-all illustrate the same process. Vector populations, infestation rates, and rates of disease transmission, can be reduced. The real problem is not in achieving the initial reduction, but in subsequently either driving the disease to extinction or maintaining it below acceptable levels. And this problem takes us beyond the simple analysis of interventions, into the complex realms of population behaviour set in its political, social and economic context. It seems that we have been too rarely concerned to plan and implement the long term surveillance and selective interventions that are required to translate initial gains into real success. In biological terms, we tend to ignore the complexity and robustness of vector populations and disease transmission cycles, especially their varied capacity to recover from interference. Moreover, in socio-political terms, a reduced problem-even one representing potential for future catastrophe-tends to claim less priority than present problems, even though premature redeployment of resources may abnegate gains already achieved. The problem is strongly compounded by methods of economic analysis where the benefits of avoiding future problems are strongly discounted in favour of short-term temporary gains. This paper seeks to open discussion on these long-term planning issues.

Animals↗

Molecular weight analysis of isopenicillin N synthase by electrospray mass spectrometry.

The use of electrospray mass spectrometry as a tool in analytical biochemistry was illustrated by determination of the molecular weights of wildtype and recombinant isopenicillin N synthase (IPNS). The molecular weight of recombinant IPNS produced using an expression system which generated soluble protein was found to be between 38,364 and 38,376 Da, ca 60 mass units higher than that of the wildtype material, consistent with the presence of an additional N-terminal glycine in the former. Observed molecular weights were all ca 70 Da higher than that calculated from sequence information, consistent with the complexion of a partially hydrated iron atom to the enzyme during analysis.

Escherichia coli↗

Acyl coenzyme A: 6-aminopenicillanic acid acyltransferase from Penicillium chrysogenum and Aspergillus nidulans.

A study of the final stages of the biosynthesis of the penicillins in Penicillium chrysogenum has revealed two types of enzyme. One hydrolyses phenoxymethyl penicillin to 6-aminopenicillanic acid (6-APA). The other, also obtained from Aspergillus nidulans, transfers a phenylacetyl group from phenylacetyl CoA to 6-APA. The acyltransferase, purified to apparent homogeneity, had a molecular mass of 40 kDa. It also catalyses the conversion of isopenicillin N (IPN) to benzylpenicillin (Pen G) and hydrolyses IPN to 6-APA. In the presence of SDS it dissociates, with loss of activity, into fragments of ca 30 and 10.5 kDa, but activity is regained when these fragments recombine in the absence of SDS.

Acyl Coenzyme A↗

High level expression in Escherichia coli of a fungal gene under the control of strong promoters.

A recent report (Patino et al., (1989) FEMS Microbiol. Lett. 58, 139-144) described the low level expression, in Escherichia coli, of the Isopenicillin N Synthase (IPNS) gene from Cephalosporium acremonium under the control of strong promoters. We report here our work on the expression of the IPNS gene. Plasmids containing the IPNS gene under the control of the trp or trc promoters directed synthesis of high levels of active IPNS in E. coli. Constitutive and inductive high level IPNS expression systems have been developed. Importantly, the expression vectors do not encode beta-lactamase so IPNS activity can be determined directly by biological assays. Analysis by nmr verified that the IPNS produced from these expression systems catalysed the conversion of delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (LLD-ACV) to isopenicillin N in high yield.

Acremonium↗

[Estimate of the incidence rates of chronic parasitosis and infections based on the prevalence: Chagas disease in Latin America].

A simple method is described for using prevalence data to estimate the incidence of chronic infections. The incidence rate is estimated as the prevalence rate multiplied by the crude birth rate. The method is applicable to infections which are detectable for life and which have little effect on mortality. Strictly, it is valid only if infection occurs at or shortly after birth, but we show that little error results if infections occur gradually over the first two decades of life. A method of refining the incidence estimate, when age-specific prevalence data are available, is also given. The methods are illustrated using data on Chagas' disease in Latin America.

Age Factors↗

Population dynamics of Triatoma infestans under natural climatic conditions in the Argentine Chaco.

Using experimental chicken houses at a site in central Argentina where the bug Triatoma infestans (Klug) is endemic, nine populations of this vector of Chagas disease were monitored during a 34-month period. Bug populations with four chickens as hosts were consistently larger than those with two chickens as hosts. Age structure of the bug population followed a similar pattern irrespective of the initial age structure. Egg to adult mortality was consistently around 98.5% and there was no consistent evidence for density-dependent mortality. There was some evidence for density dependence in fecundity and recruitment rates, but these were heavily constrained by low temperatures during the winter months. Nymphal development rates correlated most strongly with mean minimum temperatures rather than with mean maximum temperatures. We conclude that vector control using insecticides against this species would be most effective at the onset of winter, when recovery of any surviving populations would be inhibited by low temperatures.

Animals↗

Parasitology Today readership survey.

Our February readership survey gave interesting information, and some fairly universal cris de coeur - especially about the lack of funds available to support field research. You were critical of the journal's delivery times - which, for various reasons, should now improve - but in amongst the compliments and undisguised flattery were some real gems. I want to thank all of you who sent in completed replies, and here I have attempted to summarize some of the most significant trends suggested by your responses.

Journal Article↗

Purification and initial characterization of an enzyme with deacetoxycephalosporin C synthetase and hydroxylase activities.

Deacetoxycephalosporin C synthetase (expandase) from Cephalosporium acremonium (Acremonium chrysogenum) was purified to near homogeneity as judged by SDS/polyacrylamide-gel electrophoresis. The enzyme (Mr about 40,000) exhibited a pH optimum around 7.5. It required 2-oxoglutarate (Km 0.04 mM), Fe2+ and O2 as cofactors, and ascorbate and dithiothreitol were necessary for maximum activity. It was stable for over 4 weeks at -70 degrees C in the presence of 1 mM-dithiothreitol. Activity was inhibited by the thiol-quenching reagent N-ethylmaleimide, the metal-ion-chelating reagent bathophenanthroline, and NH4HCO3. The highly purified enzyme also showed deacetoxycephalosporin C hydroxylase (deacetylcephalosporin C synthetase) activity, indicating that both expandase and hydroxylase activities are properties of a single protein. These activities could not be separated by ion-exchange, dye-ligand, gel-filtration or hydrophobic chromatography. A beta-sulphoxide and a 3 beta-methylene hydroxy analogue of penicillin N were synthesized to test as potential intermediates in the ring-expansion reaction, Neither compound was a substrate for the enzyme. A synthetic analogue in which the 3 beta-methyl group and the 2-hydrogen atom of penicillin N were replaced by a cyclopropane ring was not a substrate but was a reversible inhibitor of the enzyme.

Acremonium↗

Density-dependent timing of defaecation by Rhodnius prolixus, and its implications for the transmission of Trypanosoma cruzi.

Transmission of Trypanosoma cruzi is crucially dependent on the timing of defaecation by their insect vectors. Experimental studies on Rhodnius prolixus nymphs revealed a negative correlation between blood meal weight and defaecation time. Bugs which fed to repletion defaecated on average 7 min after feeding, whereas bugs with interrupted feeds defaecated about 1 h later. As blood meal weight of triatomine bugs is density-dependent, these results suggest that the greatest risk of successful T. cruzi transmission would occur in recently colonized houses where the bug population is still increasing, or in houses recolonized after a vector control attempt.

Animals↗

Density-dependent perception of triatomine bug bites.

Pots containing different densities of Rhodnius prolixus were strapped on to the upper and lower arms and legs of six human volunteers. Analysis of the volunteers' perception of the bugs' probing activity showed a clear linear trend of perception according to bug density. Comparison with other results suggests that in humans as well as other vertebrate hosts, density dependent irritation from the bug bites and consequent disturbance and interruption of bugs' feeding could provide the mechanism by which bug development and population density is normally regulated.

Adult↗