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Biomedical subjects

M A Taylor

Publications and source records attributed to M A Taylor.

At least 55 records · Page 3Linked to original sources

Profiling of changes in gene expression during raspberry (Rubus idaeus) fruit ripening by application of RNA fingerprinting techniques.

Processes that contribute to the overall phenomenon of fruit ripening are not well understood for many soft fruit species, including raspberry (Rubus idaeus L.) Recent biochemical data implicate ethylene and a range of cell wall hydrolases in ripening processes. However, the genes encoding these activities, and others related to ripening, remain to be characterised. With the advent of high-throughput RNA-fingerprinting techniques it is possible to characterise rapidly the changes in gene expression during developmental processes. This paper describes the application of two RNA-fingerprinting techniques (cDNA amplified fragment length polymorphism and differential display reverse transcription-polymerase chain reaction) to the ripening fruit of Rubus idaeus. Copy-DNA tags were isolated representing 34 genes, up-regulated during fruit ripening. The expression profiles of these genes were determined by RNA-blot analysis and their sequences were compared with those in public databases. Potential roles for some of these gene products are considered, providing valuable insights into the processes that underpin fruit ripening. Many of the cDNAs isolated in this study provide tools for the biotechnological improvement of fruit quality.

Animals↗

Mechanical perturbation of the wrist during one-handed catching.

In the present study, the co-ordination of grasp and transport components of one-handed catching was examined following mechanical perturbations applied to the wrist. Six skilled catchers (mean age = 27.5 years) performed 64 trials in which tennis balls were projected at approximately 8 ms-1. The trial blocks consisted of 10 non-perturbed trials (NPTs) (baseline), and a block of 54 trials of which 20 trials were perturbed. The perturbation was in the form of a resistive force (12 N) applied via a piece of cord attached to a mechanical brake. In baseline trials participants reached maximal wrist velocity closer to the time of hand-ball contact (237 ms +/- 68) than in the perturbed (309 ms +/- 61) condition. Furthermore the wrist velocity profile of five out of six participants exhibited a double peak immediately after a perturbation. However, aperture variables such as the relative moment of final hand closure (approximately 70% of overall movement time) were not typically affected. The stability of grasp and transport coupling for one-handed catching was shown to vary from trial to trial. Skilled performers exploited redundant degrees of freedom in the motor system when faced with a sudden, unexpected change in task constraints.

Adult↗

Reduced thrombus burden with abciximab delivered locally before percutaneous intervention in saphenous vein grafts.

BACKGROUND: Existing thrombus can complicate percutaneous saphenous vein graft (SVG) intervention. Local delivery of thrombolytics has been used to reduce the thrombus burden often associated with these interventions. We sought to determine whether local delivery of a platelet glycoprotein IIb/IIIa inhibitor is feasible and can reduce thrombus burden before percutaneous SVG intervention. METHODS: We performed a multicenter pilot study of abciximab (0.25 mg/kg) given by local delivery catheter before percutaneous intervention for de novo SVG stenoses followed by intravenous infusion. All patients (n = 58) had >/=60% stenosis and Thrombolysis In Myocardial Infarction (TIMI) grade >0 flow in an SVG of 3 to 4 mm in diameter. Percent diameter stenosis, TIMI thrombus grade, and TIMI flow grade were measured before and after delivery of abciximab and after intervention. RESULTS: Median percent diameter stenosis improved from 69% to 45% (P =.0001) after local delivery, and TIMI thrombus grade >/=1 incidence reduced from 68% to 34% (P =.0001). TIMI flow grade was not significantly affected (P =.12). All patients had a successful intervention (</=50% residual stenosis). CONCLUSIONS: Local abciximab delivery before percutaneous SVG intervention is associated with significantly reduced thrombus burden, significantly improved percent diameter stenosis, and excellent acute procedural results. Further studies of this approach are warranted to define its clinical utility.

Abciximab↗

Randomized trial of the effects of cholesterol-lowering dietary treatment on psychological function.

PURPOSE: Epidemiological studies have suggested that cholesterol lowering could affect psychological functioning. This study was designed to test whether cholesterol-lowering diets adversely affect mood and cognitive function.5.2 mM [198 mg/dL]) to either a low-fat diet, a Mediterranean diet, or a waiting-list control. Cholesterol levels, psychological well-being (depression, anxiety, hostility), and cognitive function were assessed at baseline, 6 weeks, and 12 weeks. RESULTS: Total serum cholesterol levels fell significantly more in the intervention groups (8.2% reduction) than in the control group (P <0.001). All three groups showed a modest improvement in psychological well-being during the 12-week treatment period, but there were no differences among the groups. There were no between-group differences on three measures of cognitive function, but for a fourth measure, which involved the task with the greatest processing load, the two intervention groups did significantly worse (P <0.001) than the control group. The change in performance was correlated with the change in total serum cholesterol level (r = 0. 21, P = 0.01). CONCLUSIONS: Two dietary interventions that successfully lowered serum cholesterol levels had no adverse effect on mood. There was some evidence for a relative impairment in cognitive function in the treated groups in one of four cognitive tests, but additional studies will be required to determine the relevance of this finding.

Adult↗

A potato alpha-glucosidase gene encodes a glycoprotein-processing alpha-glucosidase II-like activity. Demonstration of enzyme activity and effects of down-regulation in transgenic plants.

In order to elucidate more fully the function of a potato gene (MAL1) encoding alpha-glucosidase activity, transgenic plants in which MAL1 expression was down-regulated were generated using antisense technology. In transgenic lines severely down-regulated in the expression of MAL1, total alpha-glucosidase activity was not decreased in leaves and tubers, and the contents of starch, glucose, fructose and sucrose remained unchanged in tubers. Phylogenetic analysis indicated that the MAL1 gene product was more similar to the glycoprotein-processing alpha-glucosidase II of mammalian and yeast origin than to other plant alpha-glucosidases. Using [14C-Glc]-labelled Glc2Man9GlcNAc2 as a substrate, it was demonstrated that glucosidase II activity was markedly down-regulated in microsomes isolated from tubers of four independent antisense lines studied in detail, strongly suggesting that MAL1 encodes glucosidase II activity. In field trials (but not in the glasshouse), MAL1 down-regulation produced an extremely stunted phenotype - the leaves were curled and tuber yield was decreased by 90% compared to control values. Microscopic analysis of leaves revealed significant differences between the antisense and control samples. Plants with down-regulated glucosidase II activity showed a greater degree of plasmolysis, and an increase in the size of mesophyll intracellular spaces. Analysis of cell walls also indicated changes in structure as a result of MAL1 down-regulation. In leaves from four antisense lines, the steady-state transcript level corresponding to the endoplasmic reticulum chaperone, BiP, was enhanced. This is diagnostic of stress in the endoplasmic reticulum.

Carbohydrate Metabolism↗

Teaching hospital?

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Anecdotes as Topic↗

The drug culture.

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Attitude of Health Personnel↗

Clinical and pathological observations on natural infections of cryptosporidiosis and flagellate protozoa in leopard geckos (Eublepharis macularius).

A group of adult leopard geckos (Eublepharis macularius) which had been losing weight for several months were found to be infected with Cryptosporidium species. Histological and electron microscopical investigations on the intestines of five of the lizards revealed the presence of large numbers of the developmental stages of Cryptosporidium species attached to the mucosal surface of the lower intestine, and large numbers of flagellate protozoa, suspected to be predominantly Trichomonas species, in the gut lumen. The clinical signs were attributed to the presence of one or both types of parasites.

Animals↗

The pathogenesis of experimental infections of Cryptosporidium muris (strain RN 66) in outbred nude mice.

Three groups of six-week-old nude outbred mice were orally infected with 400, 20,000 and 1,000,000 oocysts of Cryptosporidium muris (strain RN 66) per mouse, respectively. Oocysts were detected in the faeces from 10-18 days post-infection (p.i.) and continued to be shed in large numbers in all groups until the termination of the trial on day 89 p.i. Clinical signs were not observed in any of the infected mice and there was no significant effect on weight gain compared to uninfected controls. Histological examination revealed the presence of parasites confined to the glandular stomach. Parasitised gastric glands were dilated, hypertrophied and filled with numerous parasites. The glands had lost their normal cellular architecture and were lined with many undifferentiated cells. In some mice receiving the largest innoculum, the glandular mucosa was congested and the lamina propria infiltrated with eosinophils, polymorphs and lymphocytes.

Animals↗

Manipulation of S-adenosylmethionine decarboxylase activity in potato tubers. An increase in activity leads to an increase in tuber number and a change in tuber size distribution.

S-Adenosylmethionine decarboxylase (SAMDC; EC 4.1.1.50) is a key enzyme in the biosynthesis of the polyamines spermidine and spermine from putrescine and its activity is rate limiting in this pathway. Transgenic potato (Solanum tuberosum L. cv. Desiree) plants containing both sense and antisense SAMDC constructs driven by the tuber-specific patatin promoter have been generated and analysed. In sense transformants, developing tubers expressed higher steady-state levels of the SAMDC-specific transcript, had higher levels of SAMDC activity and contained significantly higher levels of spermidine than vector-transformed controls. Additionally, there was a significant shift in tuber size distribution with larger numbers of smaller tubers but no overall change in tuber yield. In developing tubers from the antisense transformed lines, there was a decrease in SAMDC transcript level, SAMDC activity and total polyamine levels. However, no obvious phenotypic effect was detected in the tuberisation physiology of the antisense lines.

Adenosylmethionine Decarboxylase↗

A phase II study of the modulation of 5-fluorouracil and folinic acid with high-dose infusional hydroxyurea in metastatic colorectal carcinoma.

BACKGROUND: Hydroxyurea (HU), an inhibitor of ribonucleotide reductase, may potentiate the activity of 5-fluorouracil (5-FU) and folinic acid (FA) by reducing the deoxyribonucleotide pool available for DNA synthesis and repair. However as HU may inhibit the formation of 5-fluoro-2-deoxyuridine-5-monophosphate (FdUMP), one of the principal active metabolites of 5-FU, the scheduling of HU may be critical. In vitro experiments suggest that administration of HU following 5-FU, maintaining the concentration in the region of 1 mM for six or more hours, significantly enhances the efficacy of 5-FU. PATIENTS AND METHODS: 5-FU/FA was given as follows: days 1 and 2-FA 250 mg/m2 (max. 350 mg) over two hours followed by 5-FU 400 mg/m2 by intravenous bolus (i.v.b.) over 15 minutes and subsequently 5-FU 400 mg/m2 infusion (ivi) over 22 hours. HU was administered on day 3 immediately after the 5-FU with 3 g i.v.b. over 15 minutes followed by 12 g ivi over 12 hours. RESULTS: Thirty patients were entered into the study. Median survival was nine months (range 1-51+ months). There were eight partial responses (28%, 95% CI: 13%-47%). The median duration of response was 6.5 (range 4-9 months). Grade 3-4 toxicities included neutropenia (grade 3 in eight patients and grade 4 in five), anaemia (grade 3 in one patient) and diarrhoea (grade 3 in two patients). Neutropenia was associated with pyrexia in two patients. Phlebitis at the infusion site occurred in five patients. The treatment was complicated by pulmonary embolism in one patient and deep venous thrombosis in another. CONCLUSION: HU administered in this schedule is well tolerated. Based on these results and those of other phase II studies, a randomised phase III study of 5-FU, FA and HU versus 5-FU and FA using the standard de Gramont schedule is recommended.

Adenocarcinoma↗

The proregion of papaya proteinase IV inhibits Colorado potato beetle digestive cysteine proteinases.

Three distinct digestive protease systems were induced in larvae of the herbivorous pest, Colorado potato beetle (CPB; Leptinotarsa decemlineata Say), and used as a model to assess the ability of the proregion of papaya proteinase IV (PPIV; glycyl endopeptidase, EC 3.4.22.25) to act as an inhibitor of insect digestive cysteine proteinases. As shown by gelatin/PAGE and complementary inhibition assays, a recombinant form of the proregion produced in Escherichia coli inhibited a fraction of the insect proteases also inhibited by the well-characterized inhibitor of cysteine proteinases, oryzacystatin I (OCI). In contrast with OCI, the inhibitory potency of the proregion was affected by an increase of the temperature, suggesting a certain alteration of its structural integrity by the insect non-target proteases. This apparent susceptibility to proteolysis was confirmed by SDS-PAGE, after challenging the proregion with the different insect extracts. As seen on gel, selective inhibition of the insect aspartate proteinase, cathepsin D, with the inhibitor pepstatin A preserved the activity of the proregion against cysteine proteinases by preventing its hydrolysis. Taken together, these observations suggest the potential of plant protease proregions as regulators of cysteine proteinases in biotechnological systems, and show the ability of protease inhibitors to preserve the integrity of 'companion' defense-related proteins from the action of insensitive proteases in target pests.

Animals↗

The isolation of genomic DNA from blackcurrant (Ribes nigrum L.).

A method is described for isolating DNA of high molecular mass (M(r)) from blackcurrant and other softfruit species. Following a hexacethylytimethyl ammonium bromide (CTAB)-based extraction procedure, samples are treated with a glycosidic hydrolase mixture and RNase, and then purified. The suitability of this DNA for Southern analysis and genomic-library construction is demonstrated.

DNA, Plant↗