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Biomedical subjects

G Ward

Publications and source records attributed to G Ward.

At least 19 recordsLinked to original sources
PubMed2005

A 125Te and 23Na NMR investigation of the structure and crystallisation of sodium tellurite glasses.

125Te static nuclear magnetic resonance (NMR) and 23Na and 125Te magic angle spinning (MAS) NMR have been used, in conjunction with X-ray diffraction, to examine the structure and crystallisation behaviour of glasses of composition xNa2O.(1-x)TeO2 (0.075 x 0.4). The MAS NMR 23Na spectra from the glasses are broad and featureless but shift by approximately +5 ppm with increased x, i.e. as the system becomes more ionic. The static 125Te NMR spectra show an increase in axial symmetry with increasing x, indicating a shift from predominantly [TeO4] to [TeO3] structural units. The 23Na and 125Te spectra from the crystallised samples have been fitted to obtain information on the sites in the metastable crystal phases, which are the first to form on heating and which are therefore more closely related to the glass structure than thermodynamically stable crystal phases. New sodium tellurite phases are reported, including a sodium stabilised, face centred cubic phase related to delta-TeO2; a metastable form of Na2Te4O9 containing 3 sodium and 4 tellurium sites; and a metastable form of Na2Te2O5 containing 2 sodium sites. There is evidence of oxidation of TeIV to TeVI occurring in glasses with high values of x and, at x=0.40 and 0.50 (outside the glass forming range), some sodium metatellurate (Na2TeO4) is formed at the same time as sodium metatellurite (Na2TeO3). The 125Te shift is very sensitive to environment within the sodium tellurite system, covering more than 320 ppm, with anisotropies varying from 640 to 1540 ppm. The lack of features in the 125Te spectra of the glass phases, combined with the large shift range and high but variable anisotropy, means than it is not possible to obtain a unique fit to any presumed species present. Furthermore, the chemical shift anisotropy parameters for three of the four Te sites in the Na2Te4O9 phase are found to lie outside the range used for previous simulations of glass spectra.

Journal Article↗
PubMed2001

Inactivation of lignin peroxidase during oxidation of the highly reactive substrate ferulic acid.

Ferulic acid (4-hydroxy-3-methoxycinnamic acid) (FA) was found to be a highly reactive substrate for lignin peroxidase (LIP), exhibiting a k(cat) of 41.7 s(-1). Despite the high reactivity, two modes of inactivation prevailed during the oxidation of FA. The first, H(2)O(2)-dependent inactivation, was evidenced by incomplete substrate oxidation and accumulation of LIP compound III (LIPIII), even at relatively low H(2)O(2) concentrations. This was attributed to the high turnover rate along with the inability of FA to revert LIPIII to the native state, as evidenced by pre-steady-state kinetics. H(2)O(2)-dependent inactivation could be avoided by inclusion of veratryl alcohol (VA), which efficiently reverts LIPIII to the native state. However, VA also mediated FA oxidation, and significantly decreased the reaction rate, which is unlike for previously reported VA-mediated reactions. The second mechanism of LIP inactivation was attributed to binding of phenoxy radicals or oxidation products to the enzyme and its extent directly correlated with the amount of FA consumed. This inactivation could be considerably suppressed by inclusion of gelatin. Therefore, during the oxidation of highly reactive phenolics, different kinds of protectors are required for efficient oxidation and maintaining LIP activity over time. This is of importance when considering emerging biotechnological applications for LIP.

Journal Article↗
PubMed2001

Initial steps of ferulic acid polymerization by lignin peroxidase.

The major products of the initial steps of ferulic acid polymerization by lignin peroxidase included three dehydrodimers resulting from beta-5' and beta-beta'coupling and two trimers resulting from the addition of ferulic acid moieties to decarboxylated derivatives of beta-O-4'- and beta-5'-coupled dehydrodimers. This is the first time that trimers have been identified from peroxidase-catalyzed oxidation of ferulic acid, and their formation appears to be favored by decarboxylation of dehydrodimer intermediates. After initial oxidation, the coupling reactions appear to be determined by the chemistry of ferulic acid phenoxy radicals, regardless of the enzyme and of whether the reaction is performed in vitro or in vivo. This claim is supported by our finding that horseradish peroxidase provides a similar product profile. Furthermore, two of the dehydrodimers were the two products obtained from laccase-catalyzed oxidation (Tatsumi, K. S., Freyer, A., Minard, R. D., and Bollag, J.-M. (1994) Environ. Sci. Technol. 28, 210-215), and the most abundant dehydrodimer is the most prominent in grass cell walls (Ralph, J., Quideau, S., Grabber, J. H., and Hatfield, R. D. (1994) J. Chem. Soc. Perkin Trans. 1, 3485-3498). Our results also indicate that the dehydrodimers and trimers are further oxidized by lignin peroxidase, suggesting that they are only intermediates in the polymerization of ferulic acid. The extent of polymerization appears to be dependent on the ionization potential of formed intermediates, H(2)O(2) concentration, and, probably, enzyme stability.

Chromatography, Gel↗
PubMed2001

Therapeutic effects of cysteine protease inhibition in allergic lung inflammation: inhibition of allergen-specific T lymphocyte migration.

OBJECTIVE AND DESIGN: We have evaluated the effects of the broad-spectrum cysteine protease inhibitor E64 on allergic lung inflammation in the mouse ovalbumin model of human asthma. We have also characterised membrane-associated cathepsin enzyme activity on a range of cell types. MATERIALS: Balb/C mice, E64 and CA074, various cell lines. TREATMENT: E64 was administered by subcutaneous minipump into ovalbumin-sensitised mice prior to intranasal ovalbumin challenge. The effect of E64 on ovalbumin-induced inflammation in vivo and ovalbumin-specific T cell proliferation in vitro and ex vivo was examined. Membrane-associated cathepsin activity on various cell types was measured. RESULTS: E64 treatment (0.36-0.48 mg/day) led to a significant reduction in eosinophil numbers and lung weights in the mouse model. Histological examination of lungs confirmed the anti-inflammatory effect. E64 greatly reduced ovalbumin-specific T cell numbers in the lymph nodes draining the lung following intranasal challenge whilst an accumulation of these T cells was found in the 'priming' lymph nodes. An analysis of various cells involved in lymphocyte priming and migration revealed that monocytes, dendritic cells and endothelial cells express high levels of membrane-associated cathepsin B activity. CONCLUSIONS: Since E64 is not cell permeable and does not inhibit antigen-induced T cell proliferation in vitro or in vivo, the data indicate that membrane-associated cysteine proteases, possibly cathepsin B, may regulate T lymphocyte migration in vivo.

Allergens↗
PubMed2001

Task-switching costs, Stroop-costs, and executive control: a correlational study.

Three correlational studies investigated the relationship between the time costs associated with Stroop stimuli (Stroop-costs) with the time costs associated with task-switching (switch-costs) obtained from colour-word stimuli and digit stimuli. In all studies, large and significant positive correlations were found between different measures of switch-costs. However, only small (and sometimes non-significant) correlations were obtained between the different measures of Stroop-costs and between measures of Stroop-costs and measures of switch-costs. The results are taken as evidence for the existence of some common or shared specialized mechanisms involved in task-switching, which are different from those used to overcome Stroop interference.

Adolescent↗
PubMed2001

Treatment for displaced intracapsular fracture of the proximal femur. A prospective, randomised trial in patients aged 65 to 79 years.

We performed a prospective, randomised trial comparing three treatments for displaced intracapsular fractures of the hip in 280 patients aged 65 to 79 years. The mean patient survival was significantly higher in the group undergoing reduction and internal fixation (79 months) compared with that with a cemented Thompson hemiarthroplasty or a cemented Monk bipolar hemiarthroplasty (61 months and 68 months, respectively). After three years, 32 of 93 patients (34.4%) who had undergone fixation had local complications, necessitating further intervention in 28 (30%). There were no significant differences in the functional outcome in survivors, who were reviewed annually to five years. Either reduction and internal fixation or cemented hemiarthroplasty may be offered as alternative treatments for a displaced intracapsular fracture in a mobile and mentally competent patient under the age of 80 years. The choice of procedure by the patient and the surgeon should be determined by the realisation that the use of internal fixation is associated with a 30% risk of failure requiring further surgery. If this is accepted, however, hemiarthroplasty is avoided, which, in our study has a significantly shorter mean survival time. The use of a bipolar prosthesis has no significant advantage.

Aged↗
PubMed2000

Thymic stress in artificially reared and maternally reared rat pups.

It is well documented that the hypothalamic-pituitary-adrenal (HPA) axis influences immunological responses to stress. Maternal factors have been shown to be necessary for appropriate modulation of the HPA axis in the developing rat. The purpose of this study was to determine whether artificially reared (AR) infant rat pups (a procedure whereby infant rats are gastrostomized and reared independently of maternal factors) have an altered function of the HPA axis in terms of thymocyte apoptosis (programmed cell death) and other indices of thymic stress. AR and maternally reared (MR) Long-Evans rat pups were randomized to control, fasted, stressed, and fasted+stressed treatment groups, as well as an unhandled, MR naive group that served as a baseline control. AR rat pups were significantly heavier than MR (p<0.001). AR rat pups had significantly lighter thymuses than did the MR pups (p<0.001) and fasted pups had significantly lighter thymuses than unfasted pups, regardless of whether they were in the AR or MR condition (p<0.005). AR pups had significantly lower thymic cell numbers and a greater percent of necrotic cells than did MR pups. There were no significant effects of rearing condition on the percent of apoptotic thymocytes. The thymocyte alterations observed in this study between the two rearing conditions suggest that AR reduces thymic weight and cell numbers, which may have consequences for the development of adult cellular immunity.

Animals↗
PubMed2000

Growth over 10 years following a 1-year trial of growth hormone therapy.

The growth of short children with chronic renal failure (CRF) and renal transplants was assessed over 10 years following entry into a 1-year trial of recombinant human growth hormone (rhGH) therapy. Patients were divided into three groups: 6 prepubertal patients with CRF (group 1), mean (range) age at start of trial 7.7 (5.0-10.4) years; 6 prepubertal patients with renal transplants (group 2), age 11.9 (9.5-14.6) years; and 6 pubertal patients with renal transplants (group 3), age 15.6 (14.1-18.3) years. In group 1, the mean (range) height standard deviation score (Ht SDS) increased from -2.9 (-3.7 to -2.2) to -1.9 (-2.9 to -0.5) over 4.0 (0.3-9.1) years of rhGH (P=0.04), and was -1.6 (-2.9 to -0.4) after 10 years of follow-up (NS). In group 2 Ht SDS increased from -3.3 (-4.5 to -1.9) to -2.9 (-5.4 to -0.5) over 2.7 (1.0-6.0) years and was -3.0 (-6.3 to -0.1) at final height (NS). In group 3 Ht SDS increased from -3.4 (-4.3 to -2.6) to -3.0 (-3.4 to -2.2) over 1.4 (0.2-2.3) years (NS) and was -2.5 (-3.0 to -1.9) at final height (P=0.03 from stopping rhGH to final height). Final height was attained in 13 patients, in whom Ht SDS increased from -3.2 (-4.3 to -1.9) to -2.6 (-3.9 to -0.5) on rhGH (P=0.004) and to -2.2 (-4.4 to -0.1) after stopping treatment (P=0.04). Four patients died, 2 have chronic hepatitis C, and 1 has had surgery for parathyroid adenomata. In conclusion, the majority of patients had an improvement in Ht SDS while on rhGH, which was maintained after stopping treatment.

Adolescent↗
PubMed2000

Sepsis: the critical role of iron.

Sepsis is a global problem which is exacerbated by increasing bacterial resistance to antibiotics. However, mechanisms of natural resistance can be extremely effective, and need to be exploited, but the availability of iron is critical for controlling bacterial growth. The diagnosis of sepsis and possible strategies for limiting iron availability are discussed.

Animals↗
PubMed2000

A recency-based account of the primacy effect in free recall.

Seven experiments investigated the role of rehearsal in free recall to determine whether accounts of recency effects based on the ratio rule could be extended to provide an account of primacy effects based on the number, distribution, and recency of the rehearsals of the study items. Primacy items were rehearsed more often and further toward the end of the list than middle items, particularly with a slow presentation rate (Experiment 1) and with high-frequency words (Experiment 2). Recency, but not primacy, was reduced by a filled delay (Experiment 3), although significant recency survived a filled retention interval when a fixed-rehearsal strategy was used (Experiment 4). Experimenter-presented schedules of rehearsals resulted in similar serial position curves to those observed with participant-generated rehearsals (Experiment 5) and were used to confirm the main findings in Experiments 6 and 7.

Adolescent↗
PubMed1999

Distamycin A selectively inhibits Acanthamoeba RNA synthesis and differentiation.

The effects of distamycin A on Acanthamoeba transcription, growth and differentiation were determined. Distamycin A inhibits transcription both in vitro and in vivo and can displace from DNA the transcription activator TATA binding protein promoter binding factor (TPBF). Inhibition in vivo is surprisingly selective for large rRNA precursors, 5S rRNA, profilin, S-adenosylmethionine synthetase, and extendin. Transcription from the TATA binding protein (TBP), TPBF, protein disulfide isomerase, tubulin and RNA polymerase II large subunit genes is only slightly inhibited. Moreover the rate of 5S rRNA transcription eventually recovers and exceeds that of untreated cells, while profilin transcription remains inhibited. Distamycin A inhibition is accompanied by a complex pattern of alterations to steady state levels of mRNAs. Actin, profilin and S-adenosylmethionine synthetase mRNAs are degraded, whereas mRNA encoding TBP is increased slightly in abundance. Transcription inhibition is accompanied by cessation of growth and severe morphological changes to Acanthamoeba, which are consistent with loss of production of mRNA encoding cytoskeletal proteins. Distamycin A also prevents starvation-induced differentiation of Acanthamoeba, in part due to complete prevention of cellulose production and cell wall formation.

Acanthamoeba↗
PubMed1999

Development of DNA vaccines for foot-and-mouth disease, evaluation of vaccines encoding replicating and non-replicating nucleic acids in swine.

We have developed naked DNA vaccine candidates for foot-and-mouth disease (FMD), an important disease of domestic animals. The virus that causes this disease, FMDV, is a member of the picornavirus family, which includes many important human pathogens, such as poliovirus, hepatitis A virus, and rhinovirus. Picornaviruses are characterized by a small (7-9000 nucleotide) RNA genome that encodes capsid proteins, processing proteinases, and enzymes required for RNA replication. We have developed two different types of DNA vaccines for FMD. The first DNA vaccine, pP12X3C, encodes the viral capsid gene (P1) and the processing proteinase (3C). Cells transfected with this DNA produce processed viral antigen, and animals inoculated with this DNA using a gene gun produced detectable antiviral immune responses. Mouse inoculations with this plasmid, and with a derivative containing a mutation in the 3C proteinase, indicated that capsid assembly was essential for induction of neutralizing antibody responses. The second DNA vaccine candidate, pWRMHX, encodes the entire FMDV genome, including the RNA-dependent RNA polymerase, permitting the plasmid-encoded viral genomes to undergo amplification in susceptible cells. pWRMHX encodes a mutation at the cell binding site, preventing the replicated genomes from causing disease. Swine inoculated with this vaccine candidate produce viral particles lacking the cell binding site, and neutralizing antibodies that recognize the virus. Comparison of the immune responses elicited by pP12X3C and pWRMHX in swine indicate that the plasmid encoding the replicating genome stimulated a stronger immune response, and swine inoculated with pWRMHX by the intramuscular, intradermal, or gene gun routes were partially protected from a highly virulent FMD challenge.

Animals↗