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Biomedical subjects

D A Wright

Publications and source records attributed to D A Wright.

At least 19 recordsLinked to original sources
PubMed2004

The effects of sieving and spatial variability of estuarine sediment toxicity samples on sediment chemistry.

In 1998, we conducted a field-validation study of the chronic 28-day whole-sediment toxicity test with Leptocheirus plumulosus in Baltimore Harbor, MD, an area where this amphipod is indigenous. This study included an evaluation of the effect of sieving on sediment chemical concentrations and the use of field replicates, or separate grabs from the same site, which provided an estimation of within-site chemical and toxicologic variability. Six stations in Baltimore Harbor, MD, were included in this evaluation. Chemical analysis of two separate unsieved field replicates from the six sites indicated that, overall, the chemical concentrations of replicates within each site were similar, especially for metals. Organic contaminants particularly total PCBs, had the highest variability between replicates. Chemical variability did not appear to be related to differences in organic carbon content or grain size or to variability in toxicologic end points. Results supported the use of composite samples in sediment toxicity tests. In addition, in most cases, sieving had little effect on sediment chemistry. For the metals and trace elements, only selenium showed a substantial change after sieving, with some samples increasing after sieving and others decreasing. Concentrations of acid-volatile sulfide (AVS) increased 194.6% at one station after sieving, although in most other cases, AVS and simultaneously extracted metals remained relatively unchanged. As expected, concentrations of organics generally decreased after sieving, but in the majority of cases this decrease was small (i.e., coefficient of variation < or = 25%). Total benzene hexachloride and total chlordanes had the greatest changes, whereas polychlorinated biphenyl concentrations decreased at only two stations after sieving. Concentrations of polyaromatic hydrocarbons showed little change after sieving. These changes in sediment chemistry due to sieving must be viewed in the larger context of the potentially confounding effects that indigenous organisms may have on the interpretation of test results from whole-sediment toxicity tests.

Amphipoda↗
PubMed2003

The effect of Duddingtonia flagrans on trichostrongyle infections of Saanen goats on pasture.

Four groups of nine Saanen goat does with a naturally acquired mixed trichostrongylid infection were grazed on four paddocks. Two groups received a daily dose of Duddingtonia flagrans at the rate of 5 x 10(7) chlamydospores per animal per day for the 26-day grazing period. After a 19-day pasture resting period, 20 worm free 12-week-old tracer kids were introduced to the paddocks for 14 days prior to removal for worm burden analysis. Four groups of five does and four kids were drenched then turned out onto the paddocks and faecal egg count (FEC) monitored. The FEC between groups was comparable throughout the initial grazing period. There were significant reductions in number of Teladorsagia circumcincta (54.8%, P=0.004) and Haemonchus contortus (85.0%, P=0.02) worms recovered from tracer animals. FEC of animals subsequently grazing pasture were significantly reduced (P=0.036) with reductions of 44% observed 4 weeks post-turnout. No significant difference was observed after 6 weeks grazing. This trial has demonstrated the potential of D. flagrans to reduce larval numbers on pasture grazed by goats under New Zealand conditions.

Animals↗
PubMed2003

General dental practitioners' knowledge of and attitudes towards the employment of dental therapists in general practice.

OBJECTIVE: To investigate general dental practitioners' knowledge of and attitudes towards dental therapists, to ascertain the likelihood of their employment in general dental practice, what client groups they would be likely to treat, and to identify the main perceived barriers to their employment in general dental practice. METHOD: Postal questionnaire. SETTING: General dental practitioners in the county of West Sussex. SAMPLING: All dentists holding a contract to provide general dental services in West Sussex were contacted. Final sample size was 200. KEY FINDINGS: Thirty eight per cent of dentists said they would employ a therapist if legislation allowed. Main perceived barriers were cost, lack of knowledge and dentists' acceptance. CONCLUSIONS: In general dentists had a favourable attitude towards dental therapists, although there was a real lack of knowledge about their permitted duties. Most dentists felt therapists should treat children and people with special needs.

Adult↗
PubMed2002

Previous exposure to VTA amphetamine enhances cocaine self-administration under a progressive ratio schedule in a D1 dopamine receptor dependent manner.

The effect of previous exposure to amphetamine (AMPH) in the ventral tegmental area (VTA) on the subsequent self-administration of cocaine was assessed. Rats in different groups were pre-exposed to three injections into the VTA of either saline (0.5 microl/side) or AMPH (2.5 microg/0.5 microl/side). Injections were given once every third day. Starting 7-10 days after the last pre-exposure injection, rats were trained to self-administer cocaine (0.3 mg/kg/infusion) under fixed ratio 1 and 2 (FR1 and FR2) schedules and then tested under a progressive ratio (PR) schedule of reinforcement for six consecutive days. No differences between groups were observed during self-administration training under the FR schedules of reinforcement. However, when tested under the PR schedule, VTA AMPH pre-exposed rats worked more and, as a result, obtained more infusions of cocaine than saline pre-exposed rats. Rats in a separate group pre-exposed to VTA AMPH but co-infused with the D(1)-like dopamine (DA) receptor antagonist SCH23390 (0.25 microg/0.5 microl/side) did not show enhanced cocaine self-administration. These rats, as well as others pre-exposed to VTA SCH23390 alone showed levels of cocaine self-administration similar to saline pre-exposed rats. Thus, in a manner paralleling the sensitization of AMPH-induced locomotion and nucleus accumbens DA overflow, previous exposure to AMPH in the VTA leads to enhanced intravenous self-administration of cocaine and activation of D(1) DA receptors in this site during pre-exposure is necessary for the production of this effect.

Amphetamine↗
PubMed2000

Baseline metal concentration in the Asian periwinkle Littorina brevicula employed as a biomonitor to assess metal pollution in Korean coastal water.

Concentrations of Al, Fe, Mn, Cu, Zn, V, Ni, Co, Cr, Cd and Pb in the Asian periwinkle Littorina brevicula were determined from 39 sampling locations along the whole Korean coast. Metal concentrations in the periwinkle varied highly with sampling stations, but the variations could be well explained by the body size after eliminating the data exceeding the 'High' criteria. Among the stations exceeding the 'High' criteria corresponding to mean plus one standard deviation of the logarithms of the individual site mean, some stations exhibited values higher than expected from the relationship between metal body burden and body size, indicating that these locations were polluted with metals. However, several 'High' stations followed the trends of the curve, suggesting that they resulted from the effect of their small body size, not from environmental contamination. Periwinkles of similar body sizes exhibited same range of metal concentrations in their body, independent of geographical position.

Animals↗
PubMed2000

A novel point mutation in CD18 causing the expression of dysfunctional CD11/CD18 leucocyte integrins in a patient with leucocyte adhesion deficiency (LAD).

Leucocyte adhesion deficiency type 1 (LAD-1) is characterized by the incapacity of leucocytes to carry out their adhesion functions via their CD11/CD18 antigens, which are also referred to as the leucocyte integrins. The patients generally suffer from poor wound healing and recurrent bacterial and fungal infections. In severe cases, the infections are often systemic and life-threatening. A LAD patient (AW) of moderate phenotype has been identified but, unlike most other cases, the level of CD11/CD18 antigens on her leucocytes are uncharacteristically high for a LAD patient. Molecular analysis revealed that she is a compound heterozygote for CD18 mutations. She has inherited a D231H mutation from her father and a G284S mutation from her mother. By transfection studies, it was established that the G284S mutation does not support CD11/CD18 antigen expression on the cell surface. In contrast, the D231H mutation does not affect CD18 forming integrin heterodimers with the CD11 antigens on the cell surface. However, the expressed integrins with the D231H mutation are not adhesive to ligands.

Animals↗
PubMed2000

Preferential resistance of dopaminergic neurons to the toxicity of glutathione depletion is independent of cellular glutathione peroxidase and is mediated by tetrahydrobiopterin.

Depletion of glutathione in the substantia nigra is one of the earliest changes observed in Parkinson's disease (PD) and could initiate dopaminergic neuronal degeneration. Nevertheless, experimental glutathione depletion does not result in preferential toxicity to dopaminergic neurons either in vivo or in vitro. Moreover, dopaminergic neurons in culture are preferentially resistant to the toxicity of glutathione depletion, possibly owing to differences in cellular glutathione peroxidase (GPx1) function. However, mesencephalic cultures from GPx1-knockout and wild-type mice were equally susceptible to the toxicity of glutathione depletion, indicating that glutathione also has GPx1-independent functions in neuronal survival. In addition, dopaminergic neurons were more resistant to the toxicity of both glutathione depletion and treatment with peroxides than nondopaminergic neurons regardless of their GPx1 status. To explain this enhanced antioxidant capacity, we hypothesized that tetrahydrobiopterin (BH(4)) may function as an antioxidant in dopaminergic neurons. In agreement, inhibition of BH(4) synthesis increased the susceptibility of dopaminergic neurons to the toxicity of glutathione depletion, whereas increasing BH(4) levels completely protected nondopaminergic neurons against it. Our results suggest that BH(4) functions as a complementary antioxidant to the glutathione/glutathione peroxidase system and that changes in BH(4) levels may contribute to the pathogenesis of PD.

Animals↗
PubMed2000

The selective toxicity of 1-methyl-4-phenylpyridinium to dopaminergic neurons: the role of mitochondrial complex I and reactive oxygen species revisited.

1-Methyl-4-phenylpyridinium (MPP(+)) is selectively toxic to dopaminergic neurons and has been studied extensively as an etiologic model of Parkinson's disease (PD) because mitochondrial dysfunction is implicated in both MPP(+) toxicity and the pathogenesis of PD. MPP(+) can inhibit mitochondrial complex I activity, and its toxicity has been attributed to the subsequent mitochondrial depolarization and generation of reactive oxygen species. However, MPP(+) toxicity has also been noted to be greater than predicted by its effect on complex I inhibition or reactive oxygen species generation. Therefore, we examined the effects of MPP(+) on survival, mitochondrial membrane potential (DeltaPsim), and superoxide and reduced glutathione levels in individual dopaminergic and nondopaminergic mesencephalic neurons. MPP(+) (5 microM) selectively induced death in fetal rat dopaminergic neurons and caused a small decrease in their DeltaPsim. In contrast, the specific complex I inhibitor rotenone, at a dose (20 nM) that was less toxic than MPP(+) to dopaminergic neurons, depolarized DeltaPsim to a greater extent than MPP(+). In addition, neither rotenone nor MPP(+) increased superoxide in dopaminergic neurons, and MPP(+) failed to alter levels of reduced glutathione. Therefore, we conclude that increased superoxide and loss of DeltaPsim may not represent primary events in MPP(+) toxicity, and complex I inhibition alone is not sufficient to explain the selective toxicity of MPP(+) to dopaminergic neurons. Clarifying the effects of MPP(+) on energy metabolism may provide insight into the mechanism of dopaminergic neuronal degeneration in PD.

1-Methyl-4-phenylpyridinium↗
PubMed2000

Intraoperative high-dose remifentanil in a patient on naltrexone therapy.

Naltrexone hydrochloride is a synthetic opioid receptor antagonist recently used in efforts to provide rapid opioid detoxification. Other clinical uses include alleviating itch due to cholestasis or uraemia. We report a case where unrecognised naltrexone therapy for itch affected anaesthesia, resulting in high opioid requirements. We also discuss other analgesic options utilized.

Aged↗
PubMed1999

Tagging chromatin with retrotransposons: target specificity of the Saccharomyces Ty5 retrotransposon changes with the chromosomal localization of Sir3p and Sir4p.

Retrotransposon and retroviral insertions are not randomly distributed on chromosomes, suggesting that retroelements actively select integration sites. This is the case for the yeast Ty5 retrotransposons, which preferentially integrate into domains of silent chromatin at the HM loci and telomeres. Here we demonstrate that loss of Sir3p or Sir4p-components of silent chromatin-causes a greater than ninefold decrease in Ty5 targeting to the HM loci and largely randomizes chromosomal integration patterns. Strains with a deletion of SIR4 also display an approximately 10-fold increase in cDNA recombination, which is due both to the expression a- and alpha-mating-type information and the loss of Sir4p. It is known that in old yeast cells or in strains carrying the sir4-42 allele, the Sir complex relocalizes to the rDNA. About 26% of Ty5 insertions occur within the rDNA in sir4-42 strains compared with 3% in wild type. Ty5, therefore, is sensitive to changes in chromatin, indicating that retrotransposons may be useful for dissecting chromatin dynamics that occur during developmental programs such as aging.

Alleles↗
PubMed1999

Assessment of metal pollution in Onsan Bay, Korea using Asian periwinkle Littorina brevicula as a biomonitor.

Cadmium (Cd), lead (Pb), copper (Cu) and zinc (Zn) concentrations in the marine gastropod, Littorina brevicula Philippi, were determined to assess the metal pollution in Onsan Bay, Korea. Samples of L. brevicula employed as a biomonitor and seawater were collected from 12 to 20 stations of Onsan Bay in November 1997, respectively. Dissolved metal concentrations in surface seawater were highest at the station near Onsan Non-ferrous Industrial Complex: 1.15 micrograms l-1 for Cd, 2.49 micrograms l-1 for Pb, 3.75 micrograms l-1 for Cu and 23.98 micrograms l-1 for Zn. These values were 1-2 orders higher than those shown at outer regions of the Bay. Metal concentrations in the soft body of periwinkles were highly variable at different sampling locations: 0.48-27.11 micrograms g-1 for Cd, 1.41-24.91 micrograms g-1 for Pb, 57-664 micrograms g-1 for Cu and 83-246 micrograms g-1 for Zn. The values from stations near the industrial complex were higher than those expected from relationships between body sizes and metal body burdens in periwinkles collected from the whole Korean coast. Spatial distribution of metal concentrations in the periwinkle and seawater indicated that Onsan industrial complex near the Bay is the input source of these metals. Especially, Cd and Pb concentrations in the periwinkle and seawater were distinctly decreased with distance from the Onsan industrial complex. Non-essential metals such as Cd and Pb in the periwinkle showed a strong correlation with dissolved metal concentrations in seawater. Conversely, essential Cu and Zn in the periwinkle were hardly explained by those in seawater, except at the most contaminated sites.

Animals↗
PubMed1999

The IMMUTANS variegation locus of Arabidopsis defines a mitochondrial alternative oxidase homolog that functions during early chloroplast biogenesis.

Nuclear gene-induced variegation mutants provide a powerful system to dissect interactions between the genetic systems of the nucleus-cytoplasm, the chloroplast, and the mitochondrion. The immutans (im) variegation mutation of Arabidopsis is nuclear and recessive and results in the production of green- and white-sectored leaves. The green sectors contain cells with normal chloroplasts, whereas the white sectors are heteroplastidic and contain cells with abnormal, pigment-deficient plastids as well as some normal chloroplasts. White sector formation can be promoted by enhanced light intensities, but sectoring becomes irreversible early in leaf development. The white sectors accumulate the carotenoid precursor phytoene. We have positionally cloned IM and found that the gene encodes a 40.5-kD protein with sequence motifs characteristic of alternative oxidase, a mitochondrial protein that functions as a terminal oxidase in the respiratory chains of all plants. However, phylogenetic analyses revealed that the IM protein is only distantly related to these other alternative oxidases, suggesting that IM is a novel member of this protein class. We sequenced three alleles of im, and all are predicted to be null. Our data suggest a model of variegation in which the IM protein functions early in chloroplast biogenesis as a component of a redox chain responsible for phytoene desaturation but that a redundant electron transfer function is capable of compensating for IM activity in some plastids and cells.

Amino Acid Sequence↗
PubMed1998

Biotic factors modifying acute toxicity of aqueous cadmium to estuarine amphipod Leptocheirus plumulosus.

A 96-h exposure to aqueous cadmium (Cd) is the recommended reference toxicity test for 10-day sediment bioassays with the estuarine amphipod, Leptocheirus plumulosus (US EPA 1994). This water-only test was used to assess the influence of organism size, sex, and nutritional status on the sensitivity of laboratory-cultured L. plumulosus to Cd. In addition, the response of field-collected amphipods was compared to similarly sized laboratory animals to assess potential seasonal changes in Cd sensitivity. Lipid content of test organisms was measured in these seasonal experiments and those evaluating effects of nutritional status because of its potential as an indicator of physiological condition. LC50 values of laboratory animals size-sorted on nested 500-, 710-, and 1000-micron mesh sieves, increased with size class: 0.36, 0.65, and 0.88 mg Cd/L, respectively. Gravid females were less sensitive than males or mature females to aqueous Cd. Studies on the influence of the molt cycle on Cd toxicity indicated enhanced sensitivity of immediate postmolt animals that may explain some of the observed differences in Cd tolerance. Nutritional effects were investigated by comparing the sensitivity of fed and starved laboratory-reared amphipods. Starved juveniles and adults were significantly smaller than their fed counterparts and exhibited a 28-43% reduction in lipid content, respectively. However, comparison of LC50 values indicated no significant differences in sensitivity to Cd between starved and fed juveniles (0.23 vs 0.30 mg Cd/L) or adults (0.37 vs 0.52 mg Cd/L). Field-collected amphipods were typically more sensitive to Cd than laboratory animals, regardless of the season, although their lipid content varied, ranging from 6.6% in August to 13.7% in November. Results are discussed with respect to the use and interpretation of toxicity tests with this species.

Animals↗
PubMed1998

The mouse genome contains two expressed intronless retroposed pseudogenes for the sentrin/sumo-1/PIC1 conjugating enzyme Ubc9.

The ubiquitin conjugating (ubc) E2 enzyme ubc-9 conjugates the ubiquitin-like peptide sentrin/SUMO-1/PIC1 to target proteins which include the Fas antigen. We show that the mouse genome contains four copies of the ubc-9 gene. These include a structural ubc-9 gene consisting of seven exons which encode a protein identical to human ubc-9, and three intronless processed pseudogenes. The open reading frames (ORF) of two of the pseudogenes, ubc9-psi1 and ubc9-psi2, correspond to the cDNA of ubc-9 and encode for proteins which differ from ubc9 by three and one amino acid substitutions respectively. The third pseudogene, ubc9-psi3, contains many mutations and stop codons. ubc9-psi1 and ubc9-psi2 are flanked by 5'- and 3'-untranslated (UT) regions homologous to those of the structural ubc-9 gene. Both genes contain a polyA tail and direct repeats at both ends suggesting that they arose by mRNA retroposition. Both ubc9-psi1 and ubc9-psi2 are transcribed into mRNA in murine cells. In contrast to ubc9, the protein products of ubc9-psil and ubc9-psi2 fail to bind Fas and to complement an yeast conditional ubc9 mutant. These results suggest that ubc9-psi1 and ubc9-psi2 encode for proteins that may interact with targets that differ from those recognized by ubc-9.

Amino Acid Sequence↗
PubMed1998

Potential retroviruses in plants: Tat1 is related to a group of Arabidopsis thaliana Ty3/gypsy retrotransposons that encode envelope-like proteins.

Tat1 was originally identified as an insertion near the Arabidopsis thaliana SAM1 gene. We provide evidence that Tat1 is a retrotransposon and that previously described insertions are solo long terminal repeats (LTRs) left behind after the deletion of coding regions of full-length elements. Three Tat1 insertions were characterized that have retrotransposon features, including a primer binding site complementary to an A. thaliana asparagine tRNA and an open reading frame (ORF) with approximately 44% amino acid sequence similarity to the gag protein of the Zea mays retrotransposon Zeon-1. Tat1 elements have large, polymorphic 3' noncoding regions that may contain transduced DNA sequences; a 477-base insertion in the 3' noncoding region of the Tat1-3 element contains part of a related retrotransposon and sequences similar to the nontranslated leader sequence of AT-P5C1, a gene for pyrroline-5-carboxylate reductase. Analysis of DNA sequences generated by the A. thaliana genome project identified 10 families of Ty3/gypsy retrotransposons, which share up to 51 and 62% amino-acid similarity to the ORFs of Tat1 and the A. thaliana Athila element, respectively. Phylogenetic analyses resolved the plant Ty3/gypsy elements into two lineages, one of which includes homologs of Tat1 and Athila. Four families of A. thaliana elements within the Tat/Athila lineage encode a conserved ORF after integrase at a position occupied by the envelope gene in retroviruses and in some insect Ty3/gypsy retrotransposons. Like retroviral envelope genes, this ORF encodes a transmembrane domain and, in some insertions, a putative secretory signal sequence. This suggests that Tat/Athila retrotransposons may produce enveloped virions and may be infectious.

Amino Acid Sequence↗