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Biomedical subjects

D E Thompson

Publications and source records attributed to D E Thompson.

At least 55 records · Page 3Linked to original sources

The complete amino acid sequence of the Clostridium botulinum type A neurotoxin, deduced by nucleotide sequence analysis of the encoding gene.

A 26-mer oligonucleotide probe was synthesized (based on the determined amino acid sequence of the N-terminus of the Clostridium botulinum type A neurotoxin, BoNT/A) and used in Southern blot analysis to construct a restriction map of the region of the clostridial genome encompassing BoNT/A. The detailed information obtained enabled the cloning of the structural gene as three distinct fragments, none of which were capable of directing the expression of a toxic molecule. The central portion was cloned as a 2-kb PvuII-TaqI fragment and the remaining regions of the light chain and heavy chain as a 2.4-kb ScaI-TaqI fragment and a 3.4-kb HpaI-PvuII fragment, respectively. The nucleotide sequence of all three fragments was determined and an open reading frame identified, composed of 1296 codons corresponding to a polypeptide of 149 502 Da. The deduced amino acid sequence exhibited 33% similarity to tetanus toxin, with the most highly conserved regions occurring between the N-termini of the respective heavy chains. Conservation of Cys residues flanking the position at which the toxins are cleaved to yield the heavy chain and light chain allowed the tentative identification of those residues which probably form the disulphide bridges linking the two toxin subfragments.

Amino Acid Sequence↗

Physical characterisation of the replication region of the Streptococcus faecalis plasmid pAM beta 1.

The complete nucleotide (nt) sequence of a 5.1-kb EcoRI DNA restriction fragment carrying the replication region of the Streptococcus faecalis plasmid pAM beta 1 has been determined. Of the seven major open reading frames (ORF A-G) identified within this fragment, two (C and E) were shown to be encoding by in vitro transcription/translation assays. Evidence was obtained that synthesis of the polypeptide (Mr 57,380) encoded by the largest ORF (E) was essential for replication. Deletion analysis indicated that the minimum unit of DNA required for replication resided on a 2.59-kb AccI-HpaI subfragment. ORF C resided outside of this fragment and encompassed an extensive region of directly repeated nt sequence. The encoded polypeptide (Mr 30,471) was therefore composed of large tracts of reiterated amino acid sequence (11 x VDP and 35 x TEP tripeptides) which probably caused the observed anomalous electrophoretic mobility of the synthesised protein (equivalent to 61 kDa). Deletion of a 416-bp segment of DNA between unique KpnI and StyI sites caused an increase in copy number, which correlated with the in vitro production of higher levels of ORF E polypeptide. Although homology was detected between the sequenced DNA, and the replicon of a closely related streptococcal plasmid (pSM19035), none was evident to any other characterised Gram+ plasmid.

Amino Acid Sequence↗

Planning tendon paths using an interactive graphic workstation.

This study provides a technique to be used for planning tendon paths in thumb reconstruction surgery. All mathematical modeling computations are performed on a VAX 11/750 host computer and the graphic manipulation is carried out by the Evans & Sutherland PS390 color display system. The results of the simulation are stored in a log file, including the rotation angles of the joints and the location of the pulley and the insertion points as a record of the tendon transfer design for a specific hand. The methods are based on the modeling of two separate types of tendon paths that consist of straight line segments and curved segments that follow bone contours. The method further assumes that the path of the tendon will always evolve to a planar curve. By integrating this technique with an existing kinematic model of the hand derived from CT-scans, a clinically relevant method has been developed.

Computer Graphics↗

A kinematic model of the flexor tendons of the hand.

The multi-joint model is a kinematic simulation of the long flexor tendons of the fingers. The tendons modeled are the flexor pollicis longus, the flexor digitorum profundus, and the flexor digitorum superficialis. The simulated tendons are displayed on an Evans and Sutherland PS330 color graphics terminal attached to a display of articulated bones of the hand. As a user changes the position of the joints of the simulated hand, the simulation displays the new tendon path and the excursion of the tendon for the new position of the hand. The multi-joint model is one component of a comprehensive model for use in a hand biomechanics computer workstation.

Computer Graphics↗

Introduction of genes for leucine biosynthesis from Clostridium pasteurianum into C. acetobutylicum by cointegrate conjugal transfer.

A Clostridium pasteurianum gene bank was constructed in Escherichia coli, using plasmid pAT153, and several chromosomal fragments found which complemented both leuB and leuC mutations in auxotrophic E. coli K12 strains. No fragments capable of complementing leuA or leuD mutations were identified. Conjugal transfer of the leuB/leuC genes from Bacillus subtilis into two different Leu- C. acetobutylicum auxotrophic strains was elicited by their incorporation into a large plasmid cointegrate composed of the conjugal plasmid pAM beta 1 and a specially constructed gram-positive, replication-deficient plasmid, pMTL21 EC. Inheritance of the cointegrate plasmid restored one of the auxotrophic C. acetobutylicum strains to prototrophy. The second strain remained Leu-.

3-Isopropylmalate Dehydrogenase↗

Effect of age and initial infection intensity on the rate of reinfection with Trichuris trichiura after treatment.

The study examines the rate of re-acquisition of Trichuris trichiura infection after treatment in two populations, one of mixed age and the other of children with known pre-intervention infection intensity. A population living in a Caribbean village was treated with mebendazole and the rate of reacquisition of infection of four age classes (2-4, 5-10, 11-30, 30+ years) monitored over a 20-month period. The reinfection rate was higher in the child age-classes indicating either that children are more exposed to infection or that adults slowly develop a partially effective acquired immunity. A cohort of children (mean age 4.5 years) was separated into 3 intensity categories on the basis of expelled worm burdens and their rate of reacquisition of infection monitored over a 12-month period. The rate of reinfection was directly and positively associated with initial infection status. This may indicate that children with low intensity infections are consistently less exposed to infection or that they have effective immune responses. The latter conclusion, however, would imply that they had acquired this immunity early in life, and so appears to contradict the suggestion that resistance is only slowly acquired by adults. Reconciling these two conclusions may require more sophisticated immunological models than have been suggested previously for geohelminthiases.

Adolescent↗

Age-related prevalence and intensity of Trichuris trichiura infection in a St. Lucian community.

Age-related changes in the average worm burden and the prevalence of Trichuris trichiura infection, in a village community in St. Lucia, were examined by field studies based on worm expulsion techniques. Horizontal age-intensity profiles were convex in form with peak parasite loads occurring in the 2 to 15-year-old children. Prevalence is shown to be a poor indicator of changes in average worm load with age. Faecal egg counts (epg and epd) provide a qualitative measure of worm burdens since fecundity is shown to be approximately independent of worm load. The parasites were highly aggregated within the study community, with most people harbouring low burdens while a few individuals harboured very heavy burdens. Of the total parasite populations in the study sample, 84% were harboured by the 2 to 15-year-old children. Of those individuals harbouring 100 worms or more, 87% were in the 2 to 10-year-old age range. Crude estimates of population parameters (basic reproductive rate, 4-5; rate of reinfection, 90 year-1) suggest that the rate of reinfection is higher than for other helminth parasites of man. The control of morbidity and parasite transmission is discussed in the context of targeting drug treatment at the child segment of the study population.

Adolescent↗

Epidemiology and population dynamics of Ascaris lumbricoides and Trichuris trichiura infection in the same community.

The gastrointestinal helminth infection status of an age-stratified sample from a single Caribbean community was assessed using anthelmintic expulsion techniques. The same sample was re-assessed in a similar manner after a 17 month period of re-infection. The age-prevalence profile of Ascaris lumbricoides was convex while that of Trichuris trichiura was asymptotic. The age-intensity profiles of both species were convex. These differing patterns are attributed to differences in the absolute worm burdens of the 2 species. The frequency distributions of infection intensity were similar for both species, and largely independent of host age. The basic reproductive rate of A. lumbricoides (Ro = 1-1.8) was similar to that recorded elsewhere and much lower than that of T. trichiura (Ro = 4-6), implying that the latter is intrinsically more resistant to control. Individual hosts were predisposed to high (or low) intensity infection with either species, although predisposition to both species simultaneously was not conclusively demonstrated. Further studies are required to determine the cause of these observations.

Adolescent↗

Predisposition to Trichuris trichiura infection in humans.

The study examines the distribution of Trichuris trichiura infection in a village community in St Lucia, West Indies. The infection intensity of the same age-stratified population was assessed (by drug expelled worm burden and faecal egg count) at the initiation of the study, and after 17 months of reinfection following treatment. The frequency distribution of worm numbers per person was similar at both periods of sampling. There was a significant correlation between the initial infection intensity of an individual, and the intensity acquired by the same individual following the 17 month period of reinfection. This relationship was observed in a broad range of host age classes. The study provides firm evidence that individuals are predisposed to heavy (or light) T. trichiura infection.

Adolescent↗

Age-relationships of Toxocara canis seropositivity and geohelminth infection prevalence in two communities in St. Lucia, West Indies.

Sera were examined from an age-stratified sample of two Caribbean communities using the Toxocara-ELISA with larval ES antigen. Seropositivity was markedly age dependent, attaining maximal values (40 and 60%) in 5-15 year olds and declining in adults. The rate of acquisition of infection with Toxocara canis and the age-prevalence profile are similar to those of Ascaris lumbricoides and Trichuris trichiura. It is suggested that toxocariasis is likely to be prevalent in tropical areas with endemic geohelminthiasis.

Adolescent↗

Epidemiological characteristics of Toxocara canis zoonotic infection of children in a Caribbean community.

The study reports the results of a summary of the prevalence and symptomatology of paediatric toxocariasis in Anse-la-Raye, St. Lucia. The seroprevalence of Toxocara canis among the children, as determined by ELISA, was 86%, the highest level recorded to date. In contrast, the prevalence of infection in dogs was not abnormally high, although the canine population was large and unconstrained compared to that in industrial countries. The presence of infective ova in peridomestic areas and the widespread practice of pica among children in the village probably combine to enhance exposure to infection.

Animals↗

Population dynamics and chemotherapeutic control of Trichuris trichiura infection of children in Jamaica and St. Lucia.

Population dynamical parameters of Trichuris trichiura infections in children were estimated from longitudinal intensity and prevalence data from a population (n = 23) in a children's home in Jamaica. The theoretical predictions of a deterministic model incorporating these parameters were approximated to observed horizontal-age prevalence data from a naturally infected population (n = 203) of children in a St. Lucian village, and a rough estimate of the basic reproductive rate (Ro = 8-10) of T. trichiura obtained. The findings suggest that T. trichiura populations are intrinsically more difficult to control by traditional mass-treatment chemotherapy (eradication requires greater than 91% of the population to be treated every 6 months for greater than 5 years) than are populations of Ascaris, but may be more susceptible to selective chemotherapy programmes which aim to treat only the most heavily infected individuals.

Age Factors↗

Rate of expulsion of Trichuris trichiura with multiple and single dose regimens of albendazole.

The efficacy of multiple and single dose regimens of albendazole on Trichuris trichiura infection was evaluated by counting the number of worms expelled/day from two pair-matched groups of children, for nine days following therapy. The temporal patterns of worm expulsion were similar whether the children received a single 400 mg dose or two consecutive doses: no worms were passed before the second day, or after the sixth day, after intervention, and the maximum worm expulsion rate was attained on the fourth day. A second treatment six days after the first expelled no more worms. The results obtained here resemble those obtained previously with a three-day (600 mg) regimen of mebendazole in a study of heavily infected children. We conclude: that irrespective of dose, benzimidazole carbamates require the gut transit time plus 48 hours to immobilize T. trichiura; and that a single dose of albendazole is effective against light infections of T. trichiura but requires further evaluation with high intensity infections.

Albendazole↗

Population distribution of Trichuris trichiura in a community of Jamaican children.

The Trichuris trichiura worm burdens of 23 children living in a Place-of-Safety in Kingston, Jamaica, were assessed by stool collection for more than five days after treatment with mebendazole. This procedure was repeated after a seven-month period of natural re-infection. For both collections the maximum rate of worm expulsion was achieved on the fourth day after starting treatment. The worm population distributions were overdispersed and well described by the negative binomial probability model (k = 0.29) in each case. For any one individual, the number of worms passed on the first expulsion was unrelated, absolutely or relatively, to the number passed on the second. These data suggest that: knowledge of the time dependency of helminth expulsion is essential for the accurate estimation of worm burdens by this method; populations of Trichuris are more highly aggregated than those of Ascaris and may thus be more susceptible to control by selective rather than random chemotherapy; and the inherent predisposition of hosts to infection may be of minor importance in determining the distribution of worms in the population-heavily infected hosts appear no more or less likely to acquire large worm burdens on subsequent exposures.

Child↗