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Biomedical subjects

S Wright

Publications and source records attributed to S Wright.

At least 109 records · Page 6Linked to original sources
PubMed1998

Seasonality of meal patterns and hormonal correlates in red deer.

Two groups of six adult, castrated, male red deer were housed under natural daylength conditions and at ambient temperature at 57 degrees N and fed ad lib. (AL) or at a fixed rate of 50 g/kg0.75 initial liveweight per day throughout the study (restricted, R). Mean daily intakes of AL animals were higher during periods of long daylength than during short daylength (p < 0.001). The higher rates of food intake during periods of long daylength were a function of greater meal durations (p < 0.001), shorter inter-meal intervals (p < 0.001) and higher (p < 0.001) mean rates of ingestion (g/min). In both groups mean plasma concentrations of prolactin, T3, T4, and insulin-like growth factor 1 (IGF-1) were higher (p < 0.001) during long daylength than short daylength although changes in thyroid hormone profiles were much less marked in AL animals. Insulin and growth hormone (GH) profiles exhibited no consistent seasonal trend. Mean plasma concentrations of T3 were higher in AL than in R animals. Mean plasma IGF-1 concentrations during long days were consistently greater in the AL than R animals. It is concluded that the effects of seasonal changes in daylength on appetite and food intake are expressed through changes in both the duration of daylight periods per se and in underlying seasonal changes in physiology and associated meal patterns and eating rates. It is concluded that the roles of T3, IGF-1, and prolactin in the expression of seasonal changes in appetite should be investigated further and, particularly, their effects on other hormone profiles and liver and gut function.

Animals↗
PubMed1998

Molecular cloning and expression analysis of a Cryptosporidium parvum gene encoding a new member of the thrombospondin family.

The apicomplexan parasite Cryptosporidium parvum invades and multiplies primarily in the brush border cells of the intestinal mucosa causing in AIDS patients a severe diarrhoea that represents a significant contributing factor leading to death. Morphological analysis indicates that the invasion machinery of C. parvum is similar to the apical complex of other parasites of the phylum Apicomplexa. We provide here evidence indicating that C. parvum also shares with these parasites a molecule crucial for the invasion of host cells. We have cloned a 3894 bp-long C. parvum cDNA encoding a protein characterised by sequence and structural similarities with members of the thrombospondin (TSP) family previously described in apicomplexan parasites of the genera Toxoplasma, Eimeria and Plasmodium. This novel C. partum molecule, the TSP-related adhesive protein of Cryptosporidium-1 (TRAP-C1), is encoded by a single copy gene containing no introns. TRAP-C1 is localised in the apical end of C. parvum sporozoites and is structurally related to the micronemal proteins MIC2 of Toxoplasma and Etp100 of Eimeria, which are involved in host-cell attachment and/or invasion. The identification of TRAP-C1 sheds new light on the molecules possibly involved in the invasion process of intestinal cells by C. parvum. We have also analysed the sequence variation of TRAP-C1 among C. parvum isolates and in the closely related species C. wrairi.

Amino Acid Sequence↗
PubMed1998

Histochemical and ultrastructural modification of mucosal mast cell granules in parasitized mice lacking the beta-chymase, mouse mast cell protease-1.

The soluble beta-chymases mouse mast cell protease-1 (mMCP-1) and rat mast cell protease-II are predominantly expressed by intestinal mucosal mast cells (IMMCs) and may promote mucosal epithelial permeability when released during intestinal allergic hypersensitivity responses. To study the function of these chymases, we generated mice with a homozygous null mutation of the mMCP-1 gene and investigated their response to infection with the intestinal nematode Nippostrongylus brasiliensis. Whereas mMCP-2, -4, and -5 were transcribed normally, there was no transcription of the mMCP-1 gene in null (-/-) mice, nor was mature mMCP-1 protein detected in (-/-) jejunal mucosa. In contrast, levels of mMCP-1 in wild-type (+/+) jejunal mucosa increased 200- to 350-fold from 0.66 microg mMCP-1/g wet weight in uninfected mice to 129 and 229 microg/g wet weight on days 8 and 10 of infection, respectively. The kinetics of IMMC recruitment differed in -/- mice compared with +/+ controls on days 8 (P < 0.05) and 10 (P < 0.03) of infection. The IMMCs in infected -/- mice stained poorly, if at all, for esterase with naphthol AS-D chloroacetate compared with the intense staining observed in +/+ controls. Ultrastructurally, the prominent crystal intragranular structures that are found in intraepithelial +/+ IMMCs were absent from -/- IMMCs. These data show that disruption of the mMCP-1 gene leads to profound histochemical and ultrastructural changes in IMMC granules.

Animals↗
PubMed1998

The pathogenesis of experimental neosporosis in pregnant sheep.

Three groups of eight pregnant sheep were inoculated with tachyzoites of the NCl isolate of Neospora caninum at 45 (group 1), 65 (group 2) or 90 (group 3) days' gestation. A further six animals (group 4) served as controls. Fourteen of the infected ewes developed a fever, which in two cases was biphasic. In six ewes in group 1, the fetuses died and were resorbed, and in the other two the fetuses were aborted. In group 2, one ewe resorbed her fetus, six aborted dead fetuses and one produced a live lamb. In group 3, six ewes aborted and two produced one live and one stillborn lamb each. Thus, the stage of gestation influenced the outcome of infection. All but one of the ewes "seroconverted", as shown by enzyme-linked immunosorbent assay, and 10 of 13 fetal sera examined by an indirect immunofluorescent antibody test were positive. The polymerase chain reaction was also used to detect DNA of N. caninum in aborted tissues. Immunohistochemical examination showed that the parasite had invaded the placentas of all cases examined, displaying an apparent predilection for fetal chorionic epithelium and fetal placental blood vessels, as well as inducing thrombosis in some maternal caruncular blood vessels. Organisms were associated with fetal vasculitis, focal degeneration and inflammation of the chorioallantois, and widespread, severe focal necrosis in the placentome. Characteristic lesions were seen in the fetal brains, in addition to focal leucomalacia, thought to be due to anoxia resulting from the placental damage. The six control sheep in group 4 remained clinically healthy and produced normal uninfected lambs.

Animals↗
PubMed1998

Western blot analysis of the IgG responses of ruminants infected with Neospora caninum and with Toxoplasma gondii.

The IgG antibody responses of sheep, goats and cattle inoculated subcutaneously with live Neospora caninum tachyzoites of the NC1 isolate were analysed by Western blotting. Antibodies were detected against a wide range of NC1 tachyzoite antigens (6.5 to 80 kDa). The dominant antibody responses were directed against proteins at 36.5-38, 45.5-48.5, 52-53.5, 58, 58.5, 59.5, 60.5, 62, 63.5, 64, 66.5, 67, 67.5, 68.5 and 69.5 kDa, with sera from all three species. These sera were also used to probe blots of Toxoplasma gondii antigen and, while a number of protein bands were recognized, there was no consistency within or between animal species. The IgG antibody responses of sheep, goats and cattle orally infected with T. gondii oocysts of the M3 isolate were analysed by the same methods. Antibodies were detected to a range of S48 toxoplasma tachyzoite antigens (11 to 83 kDa). The dominant antibody responses were directed against proteins at 11, 16-17, 21.5, 22.5-23.5, 26-28.5, 32-35, 49.5, 50.5, 53, 54.5, 60.5 and 61 kDa, with sera from all three species. These sera were also used to probe blots of N. caninum antigen; antibody responses to numerous antigens were detected but showed little consistency within or between animal species.

Animals↗
PubMed1998

A pilot study of dermofilm in acute radiation-induced desquamative skin reactions.

Dermofilm (Innovatec, Australia Pty Ltd) is a topical preparation containing hydrophilic and lipophilic agents that enhance the barrier functions of damaged skin. It has been assessed in a pilot study of 50 patients with desquamative skin reactions to establish whether it is a suitable candidate to test against an existing, widely used alternative in a randomized controlled trial. Symptomatic improvement, compliance and healing time were the study endpoints. Symptomatic improvement occurred in 49 patients and compliance with the prescribing instructions was uniform. The range of healing times observed at all sites was large but a relationship with the size of the initial desquamated area was noted. It is concluded that a randomized trial comparing Dermofilm with a widely used and cheaper alternative would require a multicentre effort involving approximately 400 patients (200 per arm). Other trial design considerations are discussed.

Acute Disease↗
PubMed1998

Human amylin induces "apoptotic" pattern of gene expression concomitant with cortical neuronal apoptosis.

Amylin forms large beta-pleated neurotoxic oligomers but shows only 38% sequence similarity to A beta. As patterns of gene expression during neuronal apoptosis appear stimulus and cell type specific, we compared the pattern of amylin-induced gene expression in rat cortical neurons with that shown previously to be induced by A beta in order to evaluate whether these two peptides with different primary but similar secondary structure induce apoptosis similarly. Morphologic and quantitative measures of cell death show widespread apoptotic death after amylin treatment. Amylin treatment results in time- and concentration-dependent inductions of oxidative stress genes, such as cox-2 and IkappaB-alpha. "Apoptotic" genes are also induced in a time- and concentration-dependent manner, including c-jun, junB, c-fos, and fosB, followed temporally by a gene known to be modulated by these transcription factors, i.e., transin. In situ hybridization analyses show that c-fos expression is restricted largely to neurons with condensed chromatin, a hallmark of apoptosis. As these genes are not induced in all models of apoptosis, that amylin-induced neuronal death is genetically similar to that of A beta suggests that these peptides may be neurotoxic through a common mechanism.

Alzheimer Disease↗
PubMed1998

Effect of cell swelling on membrane and cytoplasmic distribution of pICln.

pICln is found ubiquitously in mammalian cells and is postulated to play a critical role in cell volume regulation. Mutagenesis studies led to the proposal that pICln is a swelling-activated anion channel. However, recent studies in Madin-Darby canine kidney cells and endothelial cells have shown that the protein is localized primarily to the cytoplasm. It has therefore been postulated that activation involves reversible translocation of pICln from the cytoplasm and insertion into the plasma membrane. We tested this hypothesis using several different approaches. Fractionation of C6 glioma cells into plasma membrane- and cytoplasm-containing fractions demonstrated that approximately 90% of the recovered pICln was confined to the cytosol. Swelling had no effect on the relative amount of protein present in the plasma membrane fraction. Immunofluorescence microscopy revealed that pICln is localized primarily, if not exclusively, to the cytoplasm of swollen and nonswollen cells. Similarly, transfection of cells with a green fluorescent protein-labeled pICln construct failed to reveal any membrane localization of the protein. These findings do not support the hypothesis that pICln is a volume regulatory anion channel activated by swelling-induced membrane insertion.

Animals↗
PubMed1998

Benefits from adding the 5-lipoxygenase inhibitor zileuton to conventional therapy in aspirin-intolerant asthmatics.

From bronchoprovocation studies and investigations of the acute effects of drugs that inhibit leukotrienes (LT), the hypothesis has emerged that leukotrienes are important mediators of airway obstruction and other symptoms in aspirin-intolerant asthma (AIA). However, it has yet not been shown if subjects with AIA respond favorably to clinical treatment with leukotriene inhibitors. Therefore, in a double-blind placebo-controlled crossover study, we examined the effects of 6 wk of treatment with the leukotriene-pathway inhibitor zileuton (600 mg, four times daily) in 40 patients with well-characterized AIA. The treatment was added to existing therapy, which included medium to high doses of inhaled (average daily dose 1,030 microg of beclomethasone or budesonide) or oral glucocorticosteroids (4 to 25 mg/d) for all but one of the patients. On top of this treated baseline, there were no significant effects of adding placebo, indicating that their asthma was kept relatively stable. However, there was an acute and chronic improvement in pulmonary function after treatment with zileuton, expressed both as increased FEV1 from baseline compared with placebo, and higher morning and evening peak expiratory flow rate (PEFR) values on zileuton treatment compared with placebo. The improvements occurred despite lower use of rescue bronchodilator with zileuton. Zileuton also diminished nasal dysfunction, which is one of the cardinal signs of AIA. There was a remarkable return of smell, less rhinorrhea, and a trend for less stuffiness and higher nasal inspiratory flow during treatment with zileuton. Zileuton caused a small but distinct reduction of bronchial hyperresponsiveness to histamine and inhibited aspirin-induced bronchoconstriction. Zileuton inhibited urinary excretion of LTE4 but did not change airway reactivity to inhaled LTD4, supporting that zileuton specifically inhibited leukotriene biosynthesis. The findings indicate that leukotrienes are important mediators of persistent airway obstruction and chronic nasal dysfunction in AIA. The study also suggests that addition of a leukotriene pathway inhibitor such as zileuton may bring about greater control of asthma than what is achieved by treatment with medium to high doses of glucocorticosteroids alone.

Adrenergic beta-Agonists↗
PubMed1998

Effect of cyclical salinity changes on cell volume and function in geukensia demissa gills

We acclimated the estuarine mussel Geukensia demissa to a regime of sinusoidal salinity cycling (12 h cycle between 100 % and 60 % seawater) and correlated changes in the volume of gill cells with changes in several indicators of the functional status of gill cells (rate of O2 consumption, ATP content and amino acid transport). There was no indication of short-term volume regulation in the gill cells of mussels acclimated to salinity cycling. When exposed to cycling salinity, cell water space consistently increased to approximately 3 ml g-1 dry mass during the cycle troughs (60 % seawater) and returned to approximately 2 ml g-1 dry mass at the cycle peaks (100 % seawater). In mussels acclimated for 2 weeks to cycling salinity, the gill contents of betaine, taurine and K+ were unchanged (approximately 240, 230 and 160 micromol g-1 dry mass, respectively) between the 60 % and 100 % seawater portions of the salinity cycle. The changes in cell volume did not appear to be associated with large perturbations in the functional status of cells. The rate of O2 consumption was approximately 100 microl O2 g-1 dry mass min-1, and ATP content was approximately 30 micromol g-1 protein, in all salinities to which mussels were exposed. Rates of uptake of taurine, leucine and phenylalanine decreased by approximately 50 % during the first sinusoidal decrease to 60 % seawater, but recovered following re-exposure to 100 % seawater. Uptake rates of all three amino acids were unaffected by any subsequent salinity cycles. These results suggest (1) that the regulation of gill cell volume is normally absent from mussels exposed to repeated, gradual salinity changes, and (2) that any effects of changes in cell volume are not severe enough to justify the energetic expenditure that would be associated with repeated regulation of cell volume. Unlike the response of gill cells to cycling salinity, there was a decrease in the solute contents of ventricles during the salinity troughs compared with the salinity peaks, suggesting that the presence of short-term volume regulation may be more critical in the ventricle.

Journal Article↗
PubMed1998

Reversible male sterility: a novel system for the production of hybrid corn.

Hybrid corn seed is traditionally produced using either mechanical/hand detasseling or cytoplasmic male sterility, or a combination of both. In recent years, the development of transgenic systems to produce hybrid seed in several crops has attracted much attention. Here we describe a transgenic mechanism for production of hybrid corn, reversible male sterility (RMS), in which the action of the cytotoxic gene used to introduce male sterility is suppressed by the application of a chemical to the plant. Reversion of the sterility allows the RMS parent to be self-fertilized, a step which overcomes the need to remove fertile sib plants prior to making the hybrid cross. The key enabling technology in RMS is the use of a plant gene promoter which is specifically induced by chemical application. We have exemplified RMS in transgenic corn plants and believe that it provides specific benefits in the production of hybrid corn seed.

Hybridization, Genetic↗
PubMed1998

Telephone follow-up: an extension of the surgical outpatient department.

A total of 112 surgical patients took part in telephone follow-up, conducted by non-medical staff, after discharge home. Successful telephone follow-up was achieved in 93% of patients at 6 weeks, 91% at 3 months and 79% at 12 months. Telephone follow-up by non-medical staff is a practical method of assessing patient outcome after surgery. Wider use of this technique would free up time in the surgical clinics, without compromising audits of outcome and purchaser demands for evidence of efficacy.

Ambulatory Surgical Procedures↗