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Biomedical subjects

M A Taylor

Publications and source records attributed to M A Taylor.

At least 37 records · Page 2Linked to original sources

The effects of stage-specific selection on the development of benzimidazole resistance in Haemonchus contortus in sheep.

Resistance to the benzimidazole (BDZ) class of anthelmintics in nematodes of sheep has become a common and global phenomenon. The rate at which the selection process and development of resistance occurs is influenced by a number of factors. Of these, the effects of stage-specific exposures to anthelmintic were investigated with a BDZ-resistant strain of Haemonchus contortus (HCR) over five parasite generations. Sheep were infected at each generation with the HCR strain and were treated with thiabendazole (TBZ), either 5 days post-infection (p.i.) (larval line), 21 days p.i. (adult line), or left untreated (no selection line). Additionally eggs from each generation were exposed to TBZ (egg line). Geometric worm burdens were calculated from post-mortem worm counts, both at the start of the study, and after the final selection studies for each of the selection lines. Egg hatch assays (EHAs) were also conducted throughout the study. All data relating to worm burdens and EHAs for each generation were analysed by linear regression to produce dose titration curves and lethal dose(50) (LD(50)) values for each of the selection lines. Over the five generations, LD(50) values on dose-response were increased and worm survival occurred at higher dose rates of TBZ irrespective of the parasite stage exposed to treatment. A similar picture was seen with ED(50) values, which showed a fluctuating but generally upward trend for each of the three selection lines. In contrast, LD(50) and ED(50) values were decreased in the no selection line, indicating some degree of reversion albeit to levels still considered to be BDZ-resistant.

Aging↗

Anthelmintic resistance detection methods.

The development of species and populations of parasitic helminths with resistance to one or more anthelmintics is an increasing problem world-wide. The majority of currently available anthelmintics used to control parasitic nematodes of cattle and sheep belong to only three main groups, the benzimidazoles, imidazothiazoles and the avermectins/milbemycins. The successful implementation of helminth control programmes designed to limit the development of resistance in nematode populations depends to some degree on the availability of effective and sensitive methods for its detection and monitoring. A variety of in vivo and in vitro tests have been developed for the detection of nematode populations resistant to the main anthelmintic groups, but each suffers to some degree from reliability, reproducibility, sensitivity and ease of interpretation. This review covers those tests that have been reported and described and highlights some of their strengths and weaknesses.

Animals↗

Attempts to immunize sheep against the scab mite, Psoroptes ovis.

Adult Psoroptes ovis were successively extracted in saline, 1% Tween, 1% Triton and 8 m urea +0.1% CHAPS. The Triton extract was separated into fractions which did or did not bind to ConA lectin. Using QuilA as adjuvant, both Triton fractions and the saline, Tween and urea extracts were tested separately as candidate protective antigens against a P. ovis challenge infestation in sheep. All induced circulating antibody responses, but the saline and Tween extracts also stimulated significant protective effects in those sheep which developed active disease. Compared to control sheep injected with adjuvant only, these immunized animals had more than two and seven-fold reductions in mean lesion areas and mite numbers, respectively.

Animals↗

Use of a high-fidelity simulator to develop testing of the technical performance of novice anaesthetists.

BACKGROUND: We used the Delphi technique to gain a consensus from 26 consultant anaesthetists about technical tasks during general anaesthesia. We then developed a technical scoring system to assess anaesthetists undertaking general anaesthesia with rapid sequence induction. METHODS: We then followed the performance of six novice anaesthetists on five occasions during their first 3 months of training. At each, visit each novice 'anaesthetized' the Human Patient Simulator at Bristol Medical Simulator Centre. For comparison seven post-fellowship anaesthetists were scored on one occasion. RESULTS: Novice scores improved significantly over the 12-week period (P<0.01). A significant difference was also found between the final novice scores and the post-fellowship subjects (P<0.05). CONCLUSIONS: These findings suggest that simulation can be used to observe and quantify technical performance.

Adolescent↗

Inhibition of the death receptor pathway by cFLIP confers partial engraftment of MHC class I-deficient stem cells and reduces tumor clearance in perforin-deficient mice.

NK cells mediate acute rejection of MHC class I-deficient bone marrow cell (BMC) grafts. However, the exact cytotoxic mechanisms of NK cells during acute BMC graft rejection are not well defined. Although the granule exocytosis pathway plays a major role in NK cell-mediated rejection, alternative perforin-independent mechanisms also exist. By analyzing the anti-apoptotic effects of cellular Fas-associated death domain-like IL-1-converting enzyme-inhibitory protein (cFLIP) overexpression, we investigated the possible role of death receptor-induced apoptosis in NK cell-mediated cytotoxicity. In the absence of perforin, we found that cFLIP overexpression reduces lysis of tumor cells by NK cells in vitro and in vivo. In addition, perforin-deficient NK cells were impaired in their ability to acutely reject cFLIP-overexpressing TAP-1 knockout stem cells. These results emphasize the importance of NK cell death receptor-mediated killing during BMC grafts in the absence of perforin.

Animals↗

1-(Arylpiperazinylamidoalkyl)-pyrimidones: orally active inhibitors of lipoprotein-associated phospholipase A(2).

The lipophilic 1-substituent in a series of 1-((amidolinked)-alkyl)-pyrimidones, inhibitors of recombinant lipoprotein-associated phospholipase A(2), has been modified to give inhibitors of high potency in human plasma and enhanced physicochemical properties. Phenylpiperazineacetamide derivative 23 shows very promising oral activity.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

The many varieties of catatonia.

About 10% of patients with severe acute psychiatric illness exhibit a cluster of motor signs (mutism, negativism, rigidity, posturing, stereotypy, staring, etc.) that are identified as the syndrome of catatonia. Catatonia responds to sedative anticonvulsant treatment (barbiturates, benzodiazepines) and to electroconvulsive therapy. These treatments raise seizure thresholds. The commonality in response indicates that catatonia, malignant catatonia, neuroleptic malignant syndrome, toxic serotonin syndrome, delirious mania, catatonic excitement, benign stupor, and oneirophrenia are best evaluated as diverse manifestations of one syndrome for clinical and neuroscience research purposes.

Acute Disease↗

Copy-DNA cloning and characterisation of a potato alpha-glucosidase: expression in Escherichia coli and effects of down-regulation in transgenic potato.

Polymerase chain reaction-based methodology was used to obtain a cDNA clone (MAL2) from potato (Solanum tuberosum L.) with the sequence characteristics of an alpha-glucosidase. Phylogenetic analysis of the deduced polypeptide encoded by this cDNA demonstrated that the most similar sequences were alpha-glucosidases and alpha-xylosidases of plant origin. The MAL2 cDNA was expressed in Escherichia coli and the recombinant MAL2 protein was affinity-purified. MAL2 catalysed the hydrolysis of a range of maltooligomers and p-nitrophenyl-alpha-D-glucopyranoside with a pH optimum of 5.5-5.7. The substrate with the lowest Km value was maltotetraose (3.7 mM). The MAL2 expression product did not catalyse the hydrolysis of xyloglucan oligosaccharides, p-nitrophenyl-alpha-D-xylopyranoside or gelatinised potato starch. MAL2 was down-regulated in transgenic potato plants using an antisense approach. In several independent transgenic antisense lines, MAL2 expression was severely down-regulated. Despite this, no decrease in total extractable alpha-glucosidase and alpha-xylosidase activity could be detected in tissues from the transgenic plants. In glasshouse trials, no visible phenotype, change in tuber yield or carbohydrate content was associated with MAL2 down-regulation. The implications of these results are discussed.

Cloning, Molecular↗

Functional characterisation of urease accessory protein G (ureG) from potato.

The activation of the nickel metalloenzyme urease is a complex process. In bacteria, several urease accessory proteins are essential for incorporation of nickel into the active centre of urease. Comparatively little is known about the activation process and the proteins involved in plants. We cloned five different cDNAs encoding isoforms of urease accessory protein G (ureG) in potato. The 5'-coding region of these cDNAs is highly polymorphic within Solanum tuberosum ssp. tuberosum, containing mainly a simple sequence repeat encoding histidine and aspartate. Mapping on an ultrahigh-density map of the potato genome and Southern blot analysis showed that the isoforms arise from allelic differences of a single-copy gene which was located on chromosome 2. Expression analysis at the mRNA and protein levels indicated the presence of ureG in almost all tissues examined, consistent with the ubiquitous expression of urease. An attempt to correlate urease activity with ureG expression levels in different tissues was made. Allelic copies of ureG were expressed in a tissue-specific manner. UreG from potato and the Klebsiella aerogenes urease operon defective in bacterial ureG were co-expressed in Escherichia coli. The plant gene complements the K. aerogenes ureG mutation, demonstrating that it encodes a urease accessory protein and indicating a structural conservation between the plant and the bacterial urease activation complexes.

Alleles↗

Compared with nibbling, neither gorging nor a morning fast affect short-term energy balance in obese patients in a chamber calorimeter.

OBJECTIVE: To test if a diet of 4.2 MJ/24 h as six isocaloric meals would result in a lower subsequent energy intake, or greater energy output than (a) 4.2 MJ/24 h as two isocaloric meals or (b) a morning fast followed by free access to food. DESIGN: Subjects were confined to the Metabolic Unit from 19:00 h on day 1 to 09:30 h on day 6. Each day they had a fixed diet providing 4.2 MJ with three pairs of meal patterns which were offered in random sequence. They were: six meals vs two meals without access to additional foods (6vs2), or six meals vs 2 meals with access to additional food (6+vs2+), or six meals vs four meals (6+vsAMFAST). In the AMFAST condition the first two meals of the day were omitted to reduce daily intake to 2.8 MJ and to create a morning fast, but additional food was accessible thereafter. Patients were confined in the chamber calorimeter from 19:00 h on day 2 until 09:00 h on day 4, and then from 19:00 h on day 4 to 09:00 h on day 6. The order in which each meal pattern was offered was balanced over time. MEASUREMENTS: Energy expenditure (chamber calorimetry), spontaneous activity (video) and energy intake (where additional foods were available) during the final 24 h of each dietary component. SUBJECTS: Ten (6vs2), eight (6+vs2+) and eight (6+vsAMFAST) women were recruited who had a BMI of greater than 25 kg/m2. RESULTS: From experiment 6vs2 the difference between energy expenditure with six meals (10.00 MJ) and two meals (9.96 MJ) was not significant (P=0.88). Energy expenditure between 23:00 h and 08:00 h ('night') was, however, significantly higher (P=0.02) with two meals (9.12 MJ/24 h) compared with six meals (8.34 MJ/24 h). The pattern of spontaneous physical activity did not differ significantly between these two meal patterns (P>0.05). Total energy intake was affected by neither meal frequency in experiment 6+vs2+ (10.75 MJ with six, 11.08 MJ with two; P=0.58) nor a morning fast in experiment 6+vsAMFAST (8.55 MJ/24 h with six, 7.60 MJ with AMFAST; P=0.40). The total diet of subjects who had a morning fast tended to have a lower percentage of total energy from carbohydrate (40%) than when they had six meals per 24 h (49%) (P=0.05). Subsequent energy balance was affected by neither meal frequency (6vs2; P=0.88, 6+vs2+; P=0.50) nor a morning fast (P=0.18). CONCLUSIONS: In the short term, meal frequency and a period of fasting have no major impact on energy intake or expenditure but energy expenditure is delayed with a lower meal frequency compared with a higher meal frequency. This might be attributed to the thermogenic effect of food continuing into the night when a later, larger meal is given. A morning fast resulted in a diet which tended to have a lower percentage of energy from carbohydrate than with no fast.

Adult↗

The role of probiotics and prebiotics in the management of diarrhoea associated with enteral tube feeding.

INTRODUCTION: Diarrhoea is a common and serious complication of enteral tube feeding, and has a range of aetiologies. Manipulation of the colonic microflora may reduce the incidence of enteral tube feeding diarrhoea via suppression of enteropathogens and production of short-chain fatty acids. Probiotics and prebiotics are commonly used during enteral tube feeding to manipulate the colonic microflora; however, their efficacy is as yet uncertain. METHODS: English-language studies investigating the pathogenesis of enteral tube feeding diarrhoea and the use of probiotics and prebiotics were identified by searching the electronic databases CINAHL, EMBASE and MEDLINE from 1980 to 2001. The bibliographies of articles obtained were searched manually. RESULTS: Only two prospective, randomized, double-blind, placebo-controlled trials have investigated the effect of a probiotic on enteral tube feeding diarrhoea; however, results are conflicting. No prospective, randomized, double-blind, placebo-controlled studies have specifically addressed the effect of a prebiotic on the incidence of enteral tube feeding diarrhoea. CONCLUSION: Theoretically, probiotics and prebiotics may be of benefit in prophylaxis against enteral tube feeding diarrhoea; however, there is currently insufficient evidence to support their routine use. Prospective, randomised, double-blind, placebo-controlled studies investigating their effect on diarrhoea are required. These observations are discussed with reference to the current literature.

Diarrhea↗

Recent developments in ectoparasiticides.

The sales and use of ectoparasiticides for the control of arthropod parasites of domestic animals constitute a major sector of the global animal health market. Animals are infected by a number of parasitic insect and acarine species causing major economic losses in production livestock, intense irritation and skin disease in companion animals, or public health issues, including bites of humans or zoonotic disease transmission. Dog and cat fleas, for example, can be a serious source of both animal and human irritation, which has led to a rapid expansion in the development of flea control products. The control of ectoparasite infections of veterinary importance still relies heavily on the use of chemicals that target the arthropod nervous system. Such compounds have suffered from a number of drawbacks, including the development of resistance and concerns over human and environmental safety. The search for safer technologies has, however, been hindered by the limited number of active target sites present in arthropods and, to some degree, by the ever-increasing costs of research and development of compounds with novel modes of action.This review provides a background to the currently available groups of ectoparasiticide compounds used in veterinary medicine and highlights some of the more recent developments including the introduction of insect growth regulators and new and improved methods of product application.

Animals↗

Placebo expectancy effects in the relationship between glucose and cognition.

The present study investigated the extent of expectancy in the ability of glucose to affect cognitive performance. Using a within-subjects design, subjects (n 26) completed four experimental sessions (in counterbalanced order and after an initial practice session) during which they were given a 500 ml drink 30 min prior to completing a cognitive assessment battery. In addition, all subjects completed a baseline practice session during which they were given no drink. During two of the sessions, subjects were given a drink containing 50 g glucose and on the other two they were given a drink containing aspartame. A balanced placebo design was used, such that for half the sessions subjects were accurately informed as to the content of the drink (glucose or aspartame), whereas in the other two sessions they were misinformed as to the content of the drink. The task battery comprised a 6 min visual analogue of the Bakan vigilance task, an immediate verbal free-recall task, an immediate verbal recognition memory task and a measure of motor speed (two-finger tapping). Blood glucose and self-reported mood were also recorded at several time points during each session. Glucose administration was found to improve recognition memory times, in direct contrast to previous findings in the literature. Glucose administration also improved performance on the Bakan task (relative to the control drink), but only in sessions where subjects were informed that they would receive glucose and not when they were told that they would receive aspartame. There were no effects either of the nature of the drink or expectancy on the other measures. These results are interpreted in terms of there being some contribution of expectancy concerning the positive effects of glucose on cognition in studies which have not used an equi-sweet dose of aspartame as a control drink.

Adolescent↗

An unusual cause of biliary stricture in a patient with neurofibromatosis type 1.

The majority of biliary strictures occur as a consequence of iatrogenic injury to the extrahepatic biliary tract, with more than 80% following cholecystectomy. The laparoscopic era has led to heightened awareness of this problem. The occurrence of an iatrogenic stricture can be particularly devastating to both patient and surgeon. The literature highlights a number of factors involved in the aetiology of such traumatic stricture formation. We report an unusual case of a Bismuth 2 stricture of the proximal common hepatic duct,occurring in a patient with type 1 neurofibromatosis, following an iatrogenic bile duct injury that occurred during a laparoscopic cholecystectomy. Histological examination of the strictured region of bile duct removed at surgery demonstrated multiple neurofibromas of varying sizes present in the submucosa. Neurofibromatosis type 1 (von Recklinghausen disease) affects the gastrointestinal tract in up to 25% of cases, and in such cases is characterized by multiple submucosal neurofibromas. We believe this is the first reported case of a biliary stricture in a patient with neurofibromatosis type 1, which appeared to be as a consequence of neurofibromas in the submucosa of the bile duct.

Adult↗