Biomedical subjects

S E Wright

Publications and source records attributed to S E Wright.

At least 19 recordsLinked to original sources

PubMed2001

Protection against vertical transmission in bovine neosporosis.

In this study we were interested to determine whether infection of cattle prior to pregnancy would afford any protection to the foetus if the dams were challenged with Neospora caninum at mid-gestation. The experiment comprised four groups of cattle: group 1, uninfected controls; group 2, inoculated with N. caninum tachyzoites 6 weeks prior to mating and then challenged with N. caninum at mid-gestation; group 3, naive cattle challenged with N. caninum at mid-gestation and group 4 were infected with N. caninum prior to mating and left unchallenged throughout pregnancy. Positive cell-mediated and humoral immune responses to N. caninum were recorded in groups 2 and 4 prior to pregnancy and in groups 2, 3 and 4 following challenge at mid-gestation. However there was a marked down regulation of the cell-mediated immune response in all groups around mid-gestation. There was a significant increase in rectal temperature response in animals in group 3 compared to group 2 following challenge but no other clinical symptoms of disease were recorded and all cattle proceeded to calving. At calving, pre-colostral blood samples were negative for antibodies to N. caninum in all the calves born to dams in groups 1, 2 and 4. In contrast, all the calves born to dams in group 3 had high levels of specific antibody to N. caninum indicating that they had been exposed to the parasite in utero. At post-mortem N. caninum DNA was detected in CNS, thymus and placental cotyledon samples in calves from group 3. All tissue samples from calves in the other 3 groups were negative for N. caninum DNA with the exception of one calf from group 2 where specific DNA was detected in a sample of spinal cord. These results suggest that the immune response generated in the dams in group 2 prior to pregnancy had protected against vertical transmission of the parasite following challenge at mid-gestation.

Animals↗

PubMed2001

Evaluation of individual components of plum odor as potential attractants for adult plum curculios.

We evaluated olfactory attraction of overwintered plum curculio (PC) adults, Conotrachelus nenuphar, to 16 individual volatile components of unripe plum odor in the laboratory using a still-air dual-choice bioassay system and in the field using baited cotton dental wicks attached to boll-weevil traps placed on the ground beneath the canopy of unsprayed apple trees. Two compounds, ethyl isovalerate and limonene, were significantly attractive in both laboratory bioassays and field experiments. In laboratory bioassays, as concentration was decreased across five orders of magnitude, a greater number of compounds elicited responses suggestive of attractancy (except at the lowest concentration). Even so, linalool, 2-hexanone, and 3-hydroxy-2-butanone were the only other compounds showing significant attractiveness in laboratory bioassays, but none of these (nor any other compounds) were significantly attractive in field assays. We suggest that the use of ethyl isovalerate and/or limonene as odor attractants offers potential to increase the efficacy of current traps for monitoring PCs immigrating into fruit orchards during spring.

Acyclic Monoterpenes↗

PubMed2001

Changes in attitudes and practices of optometrists in their management of diabetic retinopathy after the release of NHMRC guidelines. National Health and Medical Research Council.

The purpose of this study was to document attitudes and practices of Australian optometrists in their management of diabetic retinopathy prior to the release of the National Health and Medical Research Council (NHMRC) Clinical Practice Guidelines for the Management of Diabetic Retinopathy and at two time points following their release. A self-administered questionnaire was mailed to a stratified random sample of 500 Australian optometrists at the three time points. The same sample was used for the first two surveys and a new random sample was drawn for the second follow-up survey. The response to the three questionnaires was 86%, 80% and 84%, respectively. More than 90% of optometrists reported receiving a copy of the guidelines and 82% reported receiving the supplementary Retinopathy Chart. Fifty-seven per cent reported having read the guidelines at least once in entirety and 65% reported that they refer to the Retinopathy Chart at least monthly in their clinical practice. There was a significant decrease in the number of optometrists who reported that patient unwillingness to be dilated and their fear of precipitating angle closure glaucoma were moderate or major barriers to performing dilated ophthalmoscopy. Concomitantly, the percentage of optometrists who reported that they often or always perform dilated ophthalmoscopy on new patients with diabetes increased significantly from 74.5% (95% confidence limit = 70.2, 78.8) to 81.5% (95% confidence limit = 77.5, 85.5). There have been some significant changes in the self-reported management practices of optometrists in relation to diabetic retinopathy since the release of the NHMRC guidelines and Retinopathy Chart.

Attitude to Health↗

PubMed2000

Direct costs of blindness in Australia.

This study calculated the direct financial costs of blindness to the Australian government and community. Three case studies, representative of Australians with severely impaired vision, were used to calculate the annual costs associated with blindness. The costs include pensions, subsidies, concessions, equipment and services. Case I was a retired person with age-related macular degeneration, case 2 a working aged person with diabetic retinopathy, and case 3 a school student with congenital vision impairment. Sensitivity analysis was used to show the possible range of costs for each case. For case I, direct cost was $ 14686 with a range from $9749 to $22507. The cost for case 2 was $17701 ranging from $9669 to $26720. Costs associated with care and education of case 3 were $15948 ranging from $5106 to $23798. In addition to the social costs to a person who is blind, there are significant financial costs to the government and the community that will increase substantially with the ageing of the Australian population.

Aged↗

PubMed2000

Cytotoxic T lymphocytes from humans with adenocarcinomas stimulated by native MUC1 mucin and a mucin peptide mutated at a glycosylation site.

MUC1 mucin peptides stimulated cytotoxic T lymphocytes (CTL) from humans with adenocarcinomas. Peripheral blood mononuclear cells, tumor-draining lymph node cells, or tumor-infiltrating lymphocytes were stimulated using mono-nuclear cells from humans with adenocarcinomas of breast or ovary, respectively, using (a) a native MUC1 mucin tandem repeat peptide of 20 amino acids (MUC1-mtr1) plus recombinant human interleukin-2 (IL-2), (b) the mutated (T3N) MUC1-mtr1 plus IL-2, or (c) immobilized anti-CD3 plus IL-2, or (d) IL-2 alone. The CTL stimulated by each of these four conditions were predominately CD4+. However, the CTL stimulated by either the native MUC1-mtr1 or (T3N) MUC1-mtr1 showed 5-10 times greater cytotoxicity of a breast cancer cell line that expresses MUC1 compared to CTL stimulated by either anti-CD3 + IL-2 or IL-2 alone. Each incubation condition generated CTL with different variable beta gene families of T-cell receptors, implying an oligoclonal expansion of a limited CTL repertoire for each. Thus, peptide-stimulated T cells showed expression of cytotoxic cells, which was not induced by nonspecific (anti-CD3 or IL-2) stimulation.

Adenocarcinoma↗

PubMed2000

Patterns of avian seroprevalence to western equine encephalomyelitis and Saint Louis encephalitis viruses in California, USA.

Temporal and spatial changes in the enzootic activity of western equine encephalomyelitis (WEE) and St. Louis encephalitis (SLE) viruses were monitored at representative wetland study sites in the Coachella, San Joaquin, and Sacramento valleys of California from 1996 to 1998 using three methods: (1) virus isolation from pools of 50 host-seeking Culex tarsalis Coquillett females, (2) seroconversions in flocks of 10 sentinel chickens, and (3) seroprevalence in wild birds collected by mist nets and grain baited traps. Overall, 74 WEE and one SLE isolates were obtained from 222,455 Cx. tarsalis females tested in 4,988 pools. In addition, 133 and 40 seroconversions were detected in 28 chicken flocks, and 143 and 27 of 20,192 sera tested from 149 species of wild birds were positive for antibodies to WEE and SLE, respectively. WEE was active in all three valleys, whereas SLE only was detected in Coachella Valley. Seroconversions in sentinel chickens provided the most sensitive indication of enzootic activity and were correlated with seroprevalence rates in wild birds. Avian seroprevalence rates did not provide an early warning of pending enzootic activity in chickens, because positive sera from after hatching year birds collected during spring most probably were the result of infections acquired during the previous season. Few seroconversions were detected among banded recaptured birds collected during spring and early summer. Age and resident status, but not sex, were significant risk factors for wild bird infection, with the highest seroprevalence rates among after hatching year individuals of permanent resident species. Migrants (with the exception of mourning doves) and winter resident species rarely were positive. House finches, house sparrows, Gambel's quail, California quail, common ground doves, and mourning doves were most frequently positive for antibodies. The initial detection of enzootic activity each summer coincided closely with the appearance of hatching year birds of these species in our study areas, perhaps indicating their role in virus amplification. Bird species most frequently positive roosted or nested in elevated upland vegetation, sites where Cx. tarsalis host-seeking females hunt most frequently. These serosurveys provided important background information for planned host competence and chronic infection studies.

Animals↗

PubMed1999

Design and expression of a synthetic mucin gene fragment in Escherichia coli.

Adenocarcinomas of glandular tissues produce a hypoglycosylated form of a normal glycoprotein (mucin) that elicits an immune response. A tumor-specific epitope of mucin occurs in a 20-amino-acid, tandemly repeated domain of human MUC1 mucin. A synthetic gene encoding five tandem repeats of the tumor-specific epitope of human mucin (m5tr) was designed for efficient cloning and expression in Escherichia coli for subsequent use in preparing reagent quantities of the mucin 5 tandem repeat (mtr5) polypeptide. The synthetic gene was cloned in the correct reading frame into the maltose-binding protein (MBP) fusion expression vector pMAL-p2. Bacterial clones containing the mucin synthetic gene (m5tr) were shown to produce the intended recombinant fusion protein, MBP-mtr5. The fusion protein represents a significant fraction of the cell protein, 50% or more of which is secreted into the periplasm. The MBP-mtr5 protein is largely intact and easily prepared in sufficient quantity and purity for preliminary structure-function studies.

Adenocarcinoma↗

PubMed1999

In vivo expression and distribution of dense granule protein 7 (GRA7) in the exoenteric (tachyzoite, bradyzoite) and enteric (coccidian) forms of Toxoplasma gondii.

The in vivo expression and distribution of the dense granule protein GRA7 was examined in both the exoenteric (tachyzoite and bradyzoite) and enteric (coccidian) forms of Toxoplasma gondii by immunocytochemistry. There was strong staining of GRA7 in granules within all the infectious stages (tachyzoite, bradyzoite, merozoite and sporozoite). During tachyzoite development, GRA7 was secreted and was associated with the parasitophorous vacuole. In contrast, although there was staining of granules within the bradyzoites of more mature cysts, there appeared to be little staining of the tissue cyst wall or host cell. The apparent stage-specific variation in secretion of GRA7 between tachyzoites and bradyzoites was confirmed by double labelling using stage-specific markers (SAG1 and BAG1). In the enteric forms in the cat gut there was strong labelling of the PV containing early asexual and sexual stages and staining of a few granules in the apical cytoplasm of the merozoite. The positive enteric staining pattern differentiates GRA7 from the other GRA proteins (GRA1-6) which were absent in the merozoites and enteric stages. The staining pattern of GRA7 with strong staining during tachyzoite and enteric development and reduced staining in the tissue cysts is similar to that seen for NTPases. The function of GRA7 is unknown but it is unique among the dense granule proteins in being expressed in all the infectious forms of T. gondii which would point to a basic role in the vacuolar adaptations required for active parasite development.

Animals↗

PubMed1999

Enhanced HIV-1 envelope-tumor protection by a recombinant vaccinia virus expressing anchored HIV-1 gp120 lacking gp41.

A recombinant vaccinia virus (rvv) expressing, human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein, gp120, fused to a non-cleavable transmembrane protein, vvE13, elicited protection against a tumor cell line expressing HIV-1 full length envelope glycoprotein, gp160, in mice. Mice vaccinated with vvE13 exhibited a decreased incidence of tumor development and significantly smaller tumors in comparison to mice vaccinated with rvv gp160, vvE1, or a thymidine kinase minus (TK-) rvv, vSC11, or phosphate-buffered saline (PBS) injected controls. vvE13 and vvE1 also delayed tumor development, compared to vSC11 and PBS-injected controls; however, a statistical correlation could not be demonstrated due to the development of tumors in so few animals. Specificity toward HIV-1 envelope glycoprotein, was shown, since HIV-1 envelope-tumor prevention (incidence for vvE13 and size for vvE1 and vvE13 and delay for vvE1 and vvE13) was statistically superior with HIV-1 envelope expressing tumors compared to parenteral tumors. The vvE13 recombinant vaccinia virus expressing the HIV-1 envelope glycoprotein gp120 fused to a non-cleavable transmembrane protein elicits superior protection against tumors expressing the gp160 envelope glycoprotein, as compared to vvE1 expressing gp160.

Animals↗

PubMed1999

Adjuvant chemotherapy and radiation therapy for elimination of residual microscopic non-small cell lung cancer.

This study determined if patients with residual microscopic non-small cell lung cancer (NSCLC) following lung resection treated with combination chemotherapy and radiation realize prolonged survival. Ten men with microscopic NSCLC following resection were given chemotherapy and radiation therapy. Four (40%) of the ten patients were disease-free at 45 months and fully functional. Only two (20%) of the patients died of recurrent lung cancer. Of patients who died of lung cancer, recurrence occurred within five months of treatment and death occurred within one year. The findings suggest combination chemotherapy and radiation therapy delay or prevent recurrence from residual microscopic NSCLC following lung resection.

Aged↗

PubMed1998

Surface structure of human mucin using X-ray photoelectron spectroscopy.

X-ray photoelectron spectroscopy (XPS) is a surface sensitive analytical technique that measures the binding energy of electrons in atoms and molecules on the surface of a material. XPS was used to determine the distribution of the oligosaccharide side chains in the glycoprotein, MUC1 mucin. Low-resolution XPS spectra provided elemental composition of MUC1 mucin (fully glycosylated), mucin polypeptide (nonglycosylated), and carbohydrates found in mucin. The nitrogen content of MUC1 mucin was determined to be intermediate between the mucin polypeptide and the carbohydrates. Assuming a uniform distribution of carbohydrate on MUC1 mucin, the average thickness of the carbohydrate layer was calculated to be 4.9 nm using the low-resolution N 1s signals. High-resolution XPS spectra give detailed information about the chemical bonding of the surface molecules. Calculations based on the high-resolution O 1s spectra showed a carbohydrate thickness of 6.6 nm. These experimentally determined values agree reasonably well with an estimated 5 nm of carbohydrate thickness from a simple model which assume that the core protein is a rodlike molecule approximately 5 nm in diameter. Although the carbohydrate coating on the MUC1 mucin appears to be thick enough to cover the core protein entirely, fully glycosylated breast milk MUC1 mucin is susceptible to proteolytic digestion without removal of any oligosaccharide side chain, suggesting areas of exposed core protein. A possible explanation is that the oligosaccharide side chains may form patches of carbohydrate along the core protein with regions of exposed core protein.

Amino Acid Sequence↗

PubMed1998

Recombinant breast carcinoma-associated mucins expressed in a baculovirus system contain a tumor specific epitope.

Mucins are highly immunogenic glycoproteins that are abundantly expressed by breast and other adenocarcinomas. In order to progress in the understanding of the structure immunity relationship of the breast tumor associated mucin and normal tissue mucin, two forms of breast carcinoma associated mucin, muc7-BV and pem-BV, were expressed in a baculovirus expression system. The muc7-BV was constructed by inserting the seven tandem repeats of mucin core cDNA fragment into transfer vector pAc360, forming a fusion protein containing 14 amino acids of the baculovirus polyhedrin N-terminus. The pem-BV was constructed by cloning full-length mucin cDNA into the transfer vector pVL1392. The recombinant mucins were purified using immunoaffinity chromatography. The purified muc7-BV and pem-BV had molecular weights of 28 and 59 kd, respectively. No carbohydrate was detected on these recombinant mucins and is speculated to explain why both forms of recombinant mucin showed strong affinity to tumor-specific monoclonal antibody SM3. These recombinant mucins may have the potential value to develop vaccines against breast and other adenocarcinomas and to induce cytotoxic T-lymphocyte lines for immunotherapy of the same.

Adenocarcinoma↗

PubMed1998

Low dose oral interferon alpha 2a in HIV-1 seropositive patients: a double-blind, placebo-controlled trial.

Low dose oral interferon alpha has been shown to be of benefit in viral disease in animals. In a double-blind, placebo-controlled trial, 177 patients seropositive for HIV-1 were randomly assigned to receive placebo or recombinant human interferon alpha 2a (rIFN alpha). Endpoints were survival, alteration of disease classification, performance, and changes in CD4+ T cell numbers. There was a trend for improved survival in the group receiving rIFN alpha at the dose of 1.0 IU/lb. The changes in disease classification or in weight were not significantly different. Performance was improved to a greater extent (p=0.1) in the patients who received the two higher rIFN alpha dosages (1.0 IU/lb and 10.0 IU/lb) at 6 months. In addition, the CD4+ T cell count was improved only in the 1.0 IU/lb dose treatment group at 6 months. Treatment with low dose oral interferon at 1.0 IU/lb was associated with improved CD4+ T cell count, performance and a trend toward enhanced survival in HIV seropositive patients. These differences were, however, not statistically significant. A larger study, with better return rate, will be needed to determine whether low dose, oral interferon alpha is actually beneficial for these patients.

Animals↗

PubMed1998

Metallothionein, glutathione, and cystine transport in pulmonary artery endothelial cells and NIH/3T3 cells.

Both glutathione (gamma-glutamylcysteinylglycine; GSH) and the metalloprotein metallothionein (MT) are composed of approximately one-third cysteine. Both have antioxidant activity and are induced by oxidant stresses and heavy metals. Intracellular cysteine levels may depend on uptake and reduction of extracellular cystine. GSH synthesis can be limited by the activity of the xc- cystine transport system, which is induced by oxidants and other stresses. MT is induced by treatments that also increase GSH levels and may compete with GSH for intracellular cysteine. We investigated the induction of MT and GSH and cystine transport in NIH/3T3 cells and bovine pulmonary artery endothelial cells exposed to cadmium (Cd) or arsenite. Cd and arsenite increased MT and GSH in both cells. Increases in MT and GSH were accompanied by increases in cystine uptake. Inhibition of cystine transport by glutamate decreased GSH levels and blocked Cd-induced GSH increases in both cell types. MT levels were not significantly affected, suggesting that MT synthesis is less sensitive to intracellular cysteine levels than GSH synthesis.

3T3 Cells↗

PubMed1998

Comparison of the antimuscarinic and antispasmodic actions of racemic oxybutynin and desethyloxybutynin and their enantiomers with those of racemic terodiline.

Racemic oxybutynin (CAS 1508-65-2) is used clinically to treat urinary incontinence and reportedly undergoes N-deethylation to metabolites R- and/or S-desethyloxybutynin. To assess the role of these metabolites in the therapeutic effects of oxybutynin, the antimuscarinic and antispasmodic effects of RS-, R- and S-oxybutynin, RS-, R- and S-desethyloxybutynin and, for comparative purposes, RS-terodiline (CAS 7082-21-5) on isolated strips of guinea pig bladder, were examined. All of these compounds exhibited antimuscarinic activity: they competitively antagonized carbachol-induced contractions, with mean pA2 values (+/- S.E.) of 8.91 +/- 0.20, 8.80 +/- 0.27, 7.09 +/- 0.13, 8.55 +/- 0.32, 9.04 +/- 0.32, 7.31 +/- 0.35 and 6.77 +/- 0.22, respectively. Consistent with an antispasmodic action, all of the compounds produced similar inhibition of potassium-induced contraction; the mean IC50 values for reducing responses to 137.7 mmol/l potassium were between 2.22 and 5.68 mumol/l. Thus, RS- and R-oxybutynin and RS- and R-desethyloxybutynin exhibited high antimuscarinic activity relative to their antispasmodic activity, while S-oxybutynin, S-desethyloxybutynin and RS-terodiline exhibited relatively weak antimuscarinic activity. It is concluded that deethylation of oxybutynin to desethyloxybutynin does not appreciably alter its antimuscarinic or antispasmodic activity and that R- and/or S-desethyloxybutynin probably contribute significantly to the pharmacological properties of oxybutynin in humans. In addition, since the relative potency of the antimuscarinic-to-antispasmodic actions of S-oxybutynin was equivalent to that of RS-terodiline, S-oxybutynin deserves consideration for development as a single-enantiomer drug for the treatment of urinary incontinence. It may produce the same beneficial therapeutic effects as both RS-terodiline and RS-oxybutynin but, like RS-terodiline, produce a lower incidence of antimuscarinic side-effects than seen with RS-oxybutynin.

Animals↗

PubMed1997

The prevalence of Cryptosporidium parvum and C. muris in Mus domesticus, Apodemus sylvaticus and Clethrionomys glareolus in an agricultural system.

Wild mice and voles were tested for Cryptosporidium during a 2-year survey at an agricultural site in Warwickshire, United Kingdom. C. parvum and C. muris, the two cryptosporidial species known to infect mammals, were detected. Prevalence figures of 22%, 21% and 13% noted for C. parvum for Mus domesticus, Apodemus sylvaticus and Clethrionomys glareolus, respectively, were higher than those recorded for C. muris at 10%, 6% and 2%. C. parvum causes the sometimes severe diarrhoeal disease cryptosporidiosis in many hosts, but the wild rodents were asymptomatic. The discovery of C. muris in A. sylvaticus and C. glareolus confirms a wider distribution in wild rodents than has previously been reported. Rodents may represent a significant reservoir of Cryptosporidium with a high potential for infection of man and livestock due to cohabitation.

Agriculture↗

PubMed1997

Induction of cystine transport and other stress proteins by disulfiram: effects on glutathione levels in cultured cells.

Disulfiram (Antabuse) (DSF) has been reported to protect rats and other animals from the effects of hyperbaric hyperoxia at 4 to 6 ATA (atmospheres). In contrast, DSF and diethyldithiocarbamate (DDC), its metabolite, accelerate the toxic effects in rats of 100% oxygen at 1 to 2 ATA. We have examined the effects of DSF and DDC on glutathione (GSH) levels in bovine pulmonary artery endothelial cells and Chinese hamster ovary cells. Increases in intracellular GSH occurred 8 to 24 h after addition of DSF to the culture media. These increases in intracellular GSH were associated with increases in the rate of uptake of cystine into the cells. DDC was a less effective inducer of cystine uptake and increased intracellular GSH levels than was DSF. At the concentrations used, neither DDC nor DSF caused significant decreases in intracellular superoxide dismutase levels. Exogenous sulfhydryl compounds including GSH and cysteine partially blocked the induction of cystine transport by DSF or DDC, suggesting that the induction might be mediated through a sulfhydryl reaction between DSF and some cellular components. The increases in GSH in the cultured cells were not significant by 4 h of exposure. In contrast, other stress proteins including heme oxygenase are induced by 2 to 4 h after DSF addition. In previously reported in vivo studies, DSF treatment protected against hyperbaric oxygen damage after as little as 1 to 4 h pre-exposure. This suggests that effects of DSF exposure other than GSH augmentation may be responsible for the protective effects seen in vivo.

Animals↗

PubMed1995

Prevalence of specific anti-Cryptosporidium IgG, IgM and IgA antibodies in cat sera using an indirect immunofluorescence antibody test.

Sera from 258 healthy and sick domestic and feral cats were screened for specific anti-Cryptosporidium antibodies using an indirect immunofluorescence antibody test (IFA). Sera were positive for IgG, IgM and IgA antibodies in 192 (74%), 84 (32%) and 67 (26%) samples, respectively. Antibody was not detected at dilutions of 1:10 and 1:20 or greater in any of eight specific pathogen-free kittens. IgM and IgA antibody classes were more prevalent in sick than in healthy domestic cats. The presence of IgM and/or IgA antibodies indicated early infection. However, these antibody classes were present in sera from cats either positive or negative for Cryptosporidium infection by faecal examination. Pronounced polar fluorescence was observed in the sporozoites in positive samples under fluorescence microscopy. The higher prevalence of specific anti-Cryptosporidium antibodies and the absence of Cryptosporidium oocysts in faecal samples from some IFA-positive animals suggests that detection of these antibodies in sera from cats could be helpful for the diagnosis of feline cryptosporidiosis.

Animals↗