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S L Johnston

Publications and source records attributed to S L Johnston.

At least 19 recordsLinked to original sources
PubMed2006

Having it all: historical energy intakes do not generate the anticipated trade-offs in fecundity.

An axiom of life-history theory, and fundamental to our understanding of ageing, is that animals must trade-off their allocation of resources since energy and nutrients are limited. Therefore, animals cannot "have it all"--combine high rates of fecundity with extended lifespans. The idea of life-history trade-offs was recently challenged by the discovery that ageing may be governed by a small subset of molecular processes independent of fitness. We tested the "trade-off" and "having it all" theories by examining the fecundities of C57BL/6J mice placed onto four different dietary treatments that generated caloric intakes from -21 to +8.6% of controls. We predicted body fat would be deposited in relation to caloric intake. Excessive body fat is known to cause co-morbidities that shorten lifespan, while caloric restriction enhances somatic protection and increases longevity. The trade-off model predicts that increased fat would be tolerated because reproductive gain offsets shortened longevity, while animals on a restricted intake would sacrifice reproduction for lifespan extension. The responses of body fat to treatments followed our expectations, however, there was a negative relationship between reproductive performance (fecundity, litter mass) and historical intake/body fat. Our dietary restricted animals had lower protein oxidative damage and appeared able to combine life-history traits in a manner contrary to traditional expectations by having increased fecundity with the potential to have extended lifespans.

Animals↗
PubMed2005

Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children.

BACKGROUND: Asthma exacerbation is the most common cause of hospital admission in children. A study was undertaken to investigate the importance of allergen exposure in sensitised individuals in combination with viral infections and other potentially modifiable risk factors precipitating asthma hospital admission in children. METHODS: Eighty four children aged 3-17 years admitted to hospital over a 1 year period with an acute asthma exacerbation (AA) were matched for age and sex with two control groups: stable asthmatics (SA) and children admitted to hospital with non-respiratory conditions (IC). Risk factors were assessed by questionnaires and determination of allergen sensitisation, home allergen exposure, pollen exposure, and respiratory virus infection. RESULTS: Several non-modifiable factors (atopy, duration of asthma) were associated with increased risk. Among the modifiable factors, pet ownership, housing characteristics, and parental smoking did not differ between the groups. Regular inhaled corticosteroid treatment was significantly less common in the AA group than in the SA group (OR 0.2, 95% CI 0.1 to 0.6; p = 0.002). A significantly higher proportion of the AA group were virus infected (44%) and sensitised and highly exposed to sensitising allergen (76%) compared with the SA (18% and 48%) and IC groups (17% and 28%; both p<0.001). In a multiple conditional logistic regression (AA v SA), allergen sensitisation and exposure or virus detection alone were no longer independently associated with hospital admission. However, the combination of virus detection and sensitisation with high allergen exposure substantially increased the risk of admission to hospital (OR 19.4, 95% CI 3.7 to 101.5, p<0.001). CONCLUSIONS: Natural virus infection and real life allergen exposure in allergic asthmatic children increase the risk of hospital admission. Strategies for preventing exacerbations will need to address these factors.

Adolescent↗
PubMed2005

Aetiological role of viral and bacterial infections in acute adult lower respiratory tract infection (LRTI) in primary care.

BACKGROUND: Lower respiratory tract infections (LRTI) are a common reason for consulting general practitioners (GPs). In most cases the aetiology is unknown, yet most result in an antibiotic prescription. The aetiology of LRTI was investigated in a prospective controlled study. METHODS: Eighty adults presenting to GPs with acute LRTI were recruited together with 49 controls over 12 months. Throat swabs, nasal aspirates (patients and controls), and sputum (patients) were obtained and polymerase chain reaction (PCR) and reverse transcriptase polymerase chain reaction (RT-PCR) assays were used to detect Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, influenza viruses (AH1, AH3 and B), parainfluenza viruses 1-3, coronaviruses, respiratory syncytial virus, adenoviruses, rhinoviruses, and enteroviruses. Standard sputum bacteriology was also performed. Outcome was recorded at a follow up visit. RESULTS: Potential pathogens were identified in 55 patients with LRTI (69%) and seven controls (14%; p<0.0001). The identification rate was 63% (viruses) and 26% (bacteria) for patients and 12% (p<0.0001) and 6% (p = 0.013), respectively, for controls. The most common organisms identified in the patients were rhinoviruses (33%), influenza viruses (24%), and Streptococcus pneumoniae (19%) compared with 2% (p<0.001), 6% (p = 0.013), and 4% (p = 0.034), respectively, in controls. Multiple pathogens were identified in 18 of the 80 LRTI patients (22.5%) and in two of the 49 controls (4%; p = 0.011). Atypical organisms were rarely identified. Cases with bacterial aetiology were clinically indistinguishable from those with viral aetiology. CONCLUSION: Patients presenting to GPs with acute adult LRTI predominantly have a viral illness which is most commonly caused by rhinoviruses and influenza viruses.

Acute Disease↗
PubMed2004

Echocardiographic abnormalities in primary antibody deficiency.

OBJECTIVE: To document cardiac abnormalities secondary to pulmonary disease in primary antibody deficiency. PATIENTS AND METHODS: A cross sectional audit study of patients from a regional immunology centre. Subjects undergoing two dimensional and Doppler transthoracic echocardiography were reviewed. Ventricular dimensions and function, valvular competence, and estimated pulmonary artery pressure were recorded. Data were compared with clinical variables, pulmonary function tests, and thoracic computed tomography data. RESULTS: Nineteen patients with common variable immunodeficiency and one with IgG(2) subclass deficiency were included, mean age at diagnosis 37.5 years, mean estimated diagnostic delay 10.94 years. Left ventricular impairment was found in 15% and right heart dilatation in 20%. Pulmonary hypertension (mean pulmonary artery pressure >25 mm Hg) was found in 45% (9/20), graded as moderate (40-60 mm Hg) in 44% of cases. Pulmonary function was obstructive in 47% (9/19). Fifty five percent of the patients with computed tomography data within the last five years (10/18) had confirmed bronchiectasis. Patients with right heart dilatation and/or moderate pulmonary hypertension (n = 6) had a more prolonged diagnostic delay (p = 0.04) and more severe lung disease. CONCLUSION: Echocardiographic abnormalities are common in primary antibody deficiency, associated with diagnostic delay and pulmonary complications. Pulmonary hypertension should be considered in those with severe lung disease and can be confirmed by echocardiography.

Adult↗
PubMed2004

Increased frequency of detection of Chlamydophila pneumoniae in asthma.

Previous studies have suggested that chronic Chlamydophila pneumoniae infection may play a role in the pathogenesis of asthma. However, most studies have been based on serology and have been unable to differentiate acute from chronic infection. The present authors assessed the presence of acute and chronic C. pneumoniae infection in 74 spouse pairs, each consisting of one atopic asthmatic and one nonatopic nonasthmatic. Nasal secretions were sampled every 2 weeks from October to December and actively replicating C. pneumoniae infection was detected by specific RT-PCR. C. pneumoniae was detected in 31 out of 709 samples analysed, 23 (6.4%) were positive in 362 samples from asthmatic participants and in eight out of 347 (2.3%) samples from their normal spouses (with a significant difference in infection rates, 95% confidence interval: 4.2%, 1.2-7.2%). A total of 16 (22%) asthmatic and seven (9%) normal participants were positive at least once during the study. These data confirm that Chlamydophila pneumoniae infection is detected more frequently among asthmatic participants than normal control participants. Further studies are required to confirm whether infections are also present in the lower airway and whether Chlamydophila pneumoniae infection plays a role in disease pathogenesis.

Acute Disease↗
PubMed2004

Peripherally administered [Nle4,D-Phe7]-alpha-melanocyte stimulating hormone increases resting metabolic rate, while peripheral agouti-related protein has no effect, in wild type C57BL/6 and ob/ob mice.

The melanocortin system coordinates the maintenance of energy balance via the regulation of both food intake and energy expenditure. Leptin, a key adipogenic hormone involved in the regulation of energy balance is thought to act by stimulating production, in the hypothalamic arcuate nucleus, of alpha-melanocyte stimulating hormone (alphaMSH), a potent agonist of MC3/4 melanocortin receptors located in the paraventricular nucleus of the hypothalamus. Additionally leptin inhibits release of agouti-related protein (AgRP), an MC4R antagonist. During periods of caloric restriction, weight loss is not sustained because compensatory mechanisms, such as reduced resting metabolic rate (RMR) are brought into play. Understanding how these compensatory systems operate may provide valuable targets for pharmaceutical therapies to support traditional dieting approaches. As circulating leptin is reduced during caloric restriction, it may mediate some of the observed compensatory responses. In addition to decreases in circulating leptin levels, circulating AgRP is increased during fasting in rodents while alphaMSH is decreased. As central administration of AgRP depresses metabolism, we hypothesised that the peripheral rise in AgRP might be involved in signalling the depression of RMR during food restriction. We hypothesised that changes in plasma AgRP and alphaMSH may coordinate the regulation of changes in energy expenditure acting through central MC4 melanocortin receptors via the sympathetic nervous system.We show here that acute peripherally administered AgRP at supra-physiological concentrations in both lean (C57BL/6) and obese leptin-deficient (ob/ob) mice does not depress RMR, possibly because it crosses the blood-brain barrier very slowly compared with other metabolites. However, in vitro AgRP can decrease leptin secretion, by approximately 40%, from adipocytes into culture medium and may via this axis have an effect on energy metabolism during prolonged caloric restriction. In contrast, peripheral [Nle4,D-Phe7]-alpha MSH produced a large and sustained increase in resting energy expenditure (0.15 ml O2/min; P < 0.05) with a similar response in leptin-deficient ob/ob mice (0.27 ml O2/min) indicating that this effect is independent of the status of leptin production in the periphery. In both cases respiratory exchange ratio and the levels of energy expended on spontaneous physical activity were unaffected by the administration of peripheral [Nle4,D-Phe7]-alpha MSH. In conclusion, alphaMSH analogues that cross the blood-brain barrier may significantly augment dietary restriction strategies by sustaining elevated RMR.

Agouti-Related Protein↗
PubMed2004

Effect of phytase addition and dietary calcium and phosphorus levels on plasma metabolites and ileal and total-tract nutrient digestibility in pigs.

Two experiments were conducted to determine the effect of phytase on plasma metabolites and AA and energy digestibility in swine. In Exp. 1, eight barrows (surgery BW = 52 kg) were fitted with steered ileocecal cannulas. The experiment was a Latin rectangle and the treatments were 1) corn-soybean meal diet adequate in Ca and P (0.5% Ca, 0.19% available P [aP]), 2) corn-soybean meal diet with reduced Ca and P (0.4% Ca, 0.09% aP), 3) Diet 1 with 500 phytase units/kg, or 4) Diet 2 with 500 phytase units/kg. Pigs were fed twice daily to a total daily energy intake of 2.6 x maintenance (106 kcal of ME/kg of BW(0.75)). For each ileal digesta sample, digesta samples were collected for two 24-h periods and combined for each pig. The combination of supplementing with phytase and decreasing the concentration of dietary Ca and P increased average ileal AA (P < 0.02), starch (P < 0.02), GE (P < 0.04), and DM (P < 0.03) digestibilities. In Exp. 2, a feeding challenge was conducted with barrows (eight per treatment; average BW of 53 kg). The treatments consisted of a corn-soybean meal diet or corn-soybean meal diet + 500 phytase units per kilogram of diet. In the diet with no phytase, Ca and aP were at 0.50% and 0.19%, respectively, and, in the diet with phytase, Ca and aP were each decreased by 0.12%. A catheter was surgically inserted into the anterior vena cava of each pig 6 d before the start of the feeding challenge. The barrows were penned individually, and the diets were fed for 3 d before the challenge. The pigs were held without feed for 16 h, and blood samples were obtained at -60, -30, and 0 min before the pigs were fed (2% of BW). Blood samples were then collected at 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min after feeding. Glucose area under the response curve and plasma glucose, insulin, urea N, and total alpha-amino N concentrations were increased (P < 0.05) in pigs fed the diet with reduced Ca and P and the phytase addition. Area under the response curve for insulin, urea N, and total alpha-amino N; insulin:glucose; and plasma NEFA concentration, clearance, and half-life were not affected by diet. In conclusion, the combination of Ca and P reduction and phytase addition increased nutrient and energy digestibility in diets for pigs and increased plasma concentrations of glucose, insulin, urea N, and alpha-amino N.

6-Phytase↗
PubMed2004

Gamma-glutamyl transpeptidase inhibition suppresses milk protein synthesis in isolated ovine mammary cells.

The membrane spanning enzyme gamma-glutamyl transpeptidase (gamma-GT; EC 2.3.2.2) catalyses the breakdown of the tripeptide glutathione and uses free amino acids (AA) to form gamma-glutamyl transpeptidase (GT) AA that become transported into cells and converted back into free AA. gamma-Glutamyl transpeptidase activity has been shown to be important for mammary AA uptake in rodent systems, and while gamma-GT activity is high in lactating bovine mammary tissue, the role of this enzyme in milk protein synthesis of the ruminant has not been defined. The present study shows that gamma-GT activity in the ovine mammary gland, like that of rodents, increases during pregnancy and peaks early in lactation. Acivicin, a well-known inhibitor of gamma-GT, decreased gamma-GT activity in acini isolated from the ovine mammary gland and did not have secondary toxicity effects on cell viability or the uptake of radiolabeled amino-isobutyric acid. Isolated ovine acini were incubated in the presence of radiolabeled leucine, and incorporation of label into secreted protein increased during incubation. Incubation of acini with acivicin decreased milk protein secretion by 75%, indicating that gamma-GT plays an important role in milk protein production in the ruminant. Acivicin did not inhibit secretion of specific caseins but caused a global decrease in individual proteins suggesting that gamma-GT may be responsible for providing a complement of AA for milk protein synthesis.

Animals↗
PubMed2003

Misdiagnosis of hereditary angio-oedema type 1 and type 2.

BACKGROUND: Hereditary angio-oedema is a rare, life-threatening, autosomal dominant condition caused by deficiency (type 1) or dysfunction (type 2) of complement C1 inhibitor. Serological assays to measure C1 inhibitor concentration and function are widely available. However, expert interpretation may not be. OBJECTIVE: To review all cases within three NHS Trusts with a putative diagnosis of hereditary angio-oedema. METHOD: Review of laboratory results and clinical notes of 44 cases of presumed hereditary angio-oedema. RESULTS: Audit revealed that 11 of 42 (26%) cases had been incorrectly considered to have a diagnosis of hereditary angio-oedema. Two of 44 had insufficient data to assess. All 11 had low functional C1 inhibitor recorded at presentation. RESULTS: available in these 11 cases at the time of diagnosis showed a normal or borderline C4 level (>or= 50% of mean normal, in contrast to hereditary angio-oedema, where C4 was less than 40% of mean normal) indicating that the low C1 inhibitor levels were a result of sample decay. Cases incorrectly diagnosed were predominantly female and had a mean age at presentation of 40 years (compared with 22 years for type 1 hereditary angio-oedema). Six of the 11 cases were offered C1 inhibitor concentrate (pooled plasma product) as treatment. CONCLUSION: We recommend that all suspected cases of hereditary angio-oedema are reviewed, that specialist advice is sought before making the diagnosis and that the diagnosis is only made after initial abnormal serology is confirmed on a second sample.

Adolescent↗
PubMed2003

Cytokine production of RSV/PHA-stimulated tonsillar mononuclear cells: influences of age and atopy.

Links between immune responses to respiratory syncytial virus (RSV), age and atopic sensitisation are poorly understood. This study investigated the induction of target organ type-1, type-2 and proinflammatory cytokine responses to RSV and/or phytohaemagglutinin (PHA) in tonsillar mononuclear cells from children, in relation to age and atopic status. In comparison with the control medium, RSV induced production of the type-1 cytokines interferon (IFN)-gamma and interleukin (IL)-18, the pro-inflammatory cytokines IL-6, -8 and RANTES (regulated on activation, normal T-cell expressed and secreted), but not any of the type-2 cytokines IL-4, -5, -10 and -13. Induction of IL-6, -8 and RANTES, but not IFN-gamma or IL-18, were shown to be dependent on virus replication. PHA induced all except IL-12, -13, and -15. Induction of IFN-gamma, IL-6, -8, and RANTES was significantly increased in atopic children. Induction of both IFN-7 and IL-4 increased in parallel in relation to age, with no change in the IFN-gamma:IL-4 ratio. These data are compatible with the hypothesis that immature type-1 immunity during early childhood plays a role in both respiratory syncytial virus bronchiolitis and in its relationship with atopy.

Adolescent↗
PubMed2003

Effect of chromium propionate on growth, carcass traits, pork quality, and plasma metabolites in growing-finishing pigs.

Two experiments were conducted to determine the effects of dietary Cr, as Cr propionate, on growth, carcass traits, pork quality, and plasma metabolites in growing-finishing swine. Ninety-six crossbred gilts (Exp. 1; initial and final BW of 28 [SEM = 0.41] and 109 [SEM = 2.11] kg) or 144 PIC Cambrough 22 barrows (Exp. 2; initial and final BW of 26 [SEM = 0.39] and 111 [SEM = 2.52] kg) were allotted to six or four dietary treatments, respectively, with six replications and four (Exp. 1) or six (Exp. 2) pigs in each replicate pen blocked by weight in randomized complete block designs. The six dietary treatments for Exp. 1 were 1) corn-soybean meal (C-SBM), 2) C-SBM + 50 ppb Cr, 3) C-SBM + 100 ppb Cr, 4) C-SBM + 200 ppb Cr, 5) C-SBM low NE diet, and 6) C-SBM low NE diet + 200 ppb Cr. The four dietary treatments for Exp. 2 were C-SBM with 0, 100, 200, or 300 ppb Cr. Growth, carcass traits, and plasma metabolite (collected on d 29 and at each phase change) data were taken at the end of both experiments and pork quality data were taken at the end of Exp. 1. There was no effect (P > 0.10) on overall growth performance when pigs were fed graded levels of Cr (Exp. 1 and 2) or Cr in the positive control or low NE diets (Exp. 1). Longissimus muscle area, ham weight, ham fat-free lean, and total carcass lean were increased in pigs fed 200 ppb in the positive control diets but decreased in pigs fed 200 ppb Cr in the low NE diets (Cr x NE, P < 0.08). There was no effect of Cr concentration (P > 0.10) on carcass traits in Exp. 2. In Exp. 1, cook loss of a fresh or a frozen chop was decreased (P < 0.10) by 200 ppb Cr. In Exp. 1, NEFA concentration was decreased (P < 0.05) in pigs fed Cr in the positive control or low NE diets during the early-finishing period. In Exp. 2, the addition of Cr decreased NEFA (quadratic, P < 0.09) and plasma urea N (linear, P < 0.02) concentrations and tended to increase total cholesterol and high density lipoproteins (quadratic, P < 0.09). In these experiments, Cr propionate had no effect on overall growth performance, variable effects on carcass traits and plasma metabolites, and some positive effects on pork quality, especially water holding capacity of a fresh or frozen chop.

Animal Feed↗
PubMed2002

Rhinovirus-induced alterations on peripheral blood mononuclear cell phenotype and costimulatory molecule expression in normal and atopic asthmatic subjects.

BACKGROUND: Rhinovirus (RV) infection is the commonest trigger of acute asthma exacerbations; however, the immune response to these viruses and any potential implications in the mechanisms leading to asthma exacerbations are not well understood. OBJECTIVE: To assess the effects of in vitro RV infection on the phenotype and expression of costimulatory molecules on peripheral blood mononuclear cells (PBMC) from normal and atopic asthmatic subjects, as a model for RV antigen presentation. METHODS: PBMC from seven normal and seven asthmatic subjects were exposed to one infectious unit/cell of RV16 for 48 h. Surface expression of CD25, CD28, CD40, CD54, CD80, CD86 and CTLA-4 was evaluated on CD3, CD4, CD8, CD14 and CD19 PBMC subpopulations by three-colour flow cytometry. RESULTS: No changes in the percentage of CD3, CD4, CD8 or CD19 were observed. CD14 was significantly reduced by the infection and this was more pronounced in normal subjects. On Th cells CTLA-4 was increased after RV infection only in the asthmatic group. Levels of CD80 and CD86 in the control cultures were lower in the asthmatic group. RV infection induced a significant increase of CD80 on monocytes and of CD86 on B cells, which occurred in both groups but were less marked in atopic asthmatic subjects. CONCLUSION: Exposure of PBMC to RV is able to activate the antigen presentation machinery. Differences between normal and atopic asthmatic individuals are compatible with the hypothesis that an aberrant immune response to RV may be involved in the development of acute exacerbations in atopic asthmatic subjects.

Adult↗
PubMed2002

Peripheral blood CD4+ and CD8+ T cell type 1 and type 2 cytokine production in atopic asthmatic and normal subjects.

BACKGROUND: Increased production of IL-4 and IL-5 and decreased production of IFN-gamma by CD4+ T cells has been implicated in asthma pathogenesis. However, CD8+ T cells also produce type 1 and type 2 cytokines and the relative roles of CD4+ and CD8+ T cell cytokine production in asthma have not been previously studied. OBJECTIVE: To determine the production of the type 1 and type 2 cytokines by CD4+ and CD8+ T cell subsets in asthmatic and normal subjects. METHODS: Intracellular cytokine staining for IL-4, -5, -10, -13 and IFN-gamma was analysed in peripheral blood CD4+ and CD8+ T cells from 24 atopic asthmatic and 20 normal subjects. RESULTS: Both subsets of T cells produced all cytokines studied and there were no significant differences between CD4+ and CD8+ T cells in their capacity to produce either type 1 or type 2 cytokines. There were significantly increased frequencies of IFN-gamma-positive CD4+ (13.1 +/- 2.4%, vs. 7.3 +/- 1.4%) and CD8+ (20.0 +/- 2.9%, vs. 9.6 +/- 2.1%) T cells in asthmatic subjects compared with normal subjects (P < 0.05), but not in frequencies of CD4+ or CD8+ T cells staining positively for IL-4, -5, -10 or -13. CONCLUSION: The frequencies of peripheral blood CD8+ T cells producing type 1 and type 2 cytokines are comparable with the frequencies of CD4+ T cells. There was an increased frequency of IFN-gamma producing CD4+ and CD8+ T cells in asthmatic compared with normal subjects. Further studies investigating T cells derived from the airways and investigating various stages within the disease process are required to further elucidate the importance of type 2 and type 1 T cell cytokine production in the pathogenesis of human allergic disease.

Adult↗
PubMed2002

Increased aeroallergen-specific interleukin-4-producing T cells in asthmatic adults.

BACKGROUND: Asthma, atopy and some forms of respiratory syncytial virus (RSV) disease are thought to be caused by T cells making IL-4 (Th2 cells). However, not all patients with similar patterns of clinical disease have the same underlying pathogenesis and the ability to detect immunopathogenic T cells by examination of the peripheral blood remains in doubt. With the prospect of specific immunotherapy for diseases caused by T cell subsets, it is important to determine whether peripheral blood mononuclear cell (PBMC) reactivity can be used to establish the presence of immunopathogenic responses and therefore to predict therapeutic effects. OBJECTIVE: To detect IL-4 and IFN-gamma production as markers of Th1 and Th2 responses in the peripheral blood of atopic and asthmatic adults. METHODS: PBMC from 22 adult asthmatics (18 of whom were atopic) and 21 non-asthmatic volunteers (ten of whom were atopic) were stimulated with cat, birch and house dust mite allergens, human rhinovirus, RSV and recombinant chimaeric F/G protein from RSV in vitro. ELISPOT assays were used to enumerate cells producing IL-4 and IFN-gamma. RESULTS: Asthmatics had a sixfold increase in frequencies of IL-4-producing cells to cat and birch allergen (median values: 37 vs. 7 per million PBMC, P < 0.01 and 20 vs. 3 per million PBMC, P < 0.04, respectively) compared to non-asthmatics. By contrast, non-asthmatic atopics showed no specific increase in antigen-specific IL-4 responses and there was no evident correlation between skin prick test reactivity and ELISPOT results. Atopics had significantly more IFN-gamma-producing cells specific for FG than nonatopics. while IFN-gamma and IL-4 responses to other antigens were not significantly different. CONCLUSION: Enhanced IL-4 responses to non-viral aeroallergens are seen in adults with asthma, while enhanced IFN-gamma responses to viral antigen FG were see in atopics. In practical terms, ELISPOT assays for specific cytokines may provide a method that could be used to monitor antigen-specific T cell responses in peripheral blood.

Adult↗