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T J Evans

Publications and source records attributed to T J Evans.

At least 19 recordsLinked to original sources
PubMed2006

Equine endometrial fibrosis correlates with 11beta-HSD2, TGF-beta1 and ACE activities.

Endometrial periglandular fibrosis (EPF) contributes to embryonic and fetal loss in mares. Equine EPF correlates inversely with conception and successful gestation. In the modified Kenney endometrial biopsy classification system, EPF categories I, IIA, IIB, and III correspond to minimal, mild, moderate, and severe fibrosis (+/-inflammation), respectively. Paraffin sections of biopsy specimens were stained with H&E, and picrosirius red (specific for fibrillar collagens types I and III), to determine %EPCVF. Endometrial ACE-binding activity, TGF-beta1 and 11beta-HSD2 activities were also measured. Ultrastructural changes in EPF categories IIB and III endometria strongly suggested myofibroblastic transformation. ACE-binding activity was highest in EPF category IIB; however, endometrial TGF-beta1 and 11beta-HSD2 activities were significantly correlated to the severity of EPF (P<0.05). We conclude that, locally generated angiotensin II initiates the expression of TGF-beta1 resulting in myofibroblastic transformation. 11Beta-HSD2 in concert appears to modulate the severity of endometrial fibrosis.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2003

3-methylindole induces transient olfactory mucosal injury in ponies.

Response to 3-methylindole (3MI) varies among species. Mice recover from 3MI-induced bronchiolar epithelial injury but sustain persistent olfactory mucosal injury with scarring and epithelial metaplasia. In contrast, 3MI induces obliterative bronchiolitis in horses and ponies, but olfactory mucosal injury has not been reported. To evaluate the effect of 3MI on equine olfactory mucosa, ponies were dosed orally with 100 mg 3MI/kg (n = 9) or corn oil vehicle (n = 6). All ponies treated with 3MI developed obliterative bronchiolitis with mild olfactory injury. By 3 days after 3MI dosing, olfactory epithelium appeared disorganized with decreased and uneven surface height and scalloping of the basement membrane zone. Epithelial cells of Bowman's glands were hypertrophic. Proliferation of olfactory epithelium and Bowman's glands was supported by an increased mitotic index and positive immunohistochemical staining for proliferating cell nuclear antigen as compared with controls. The activity of 11beta-hydroxysteroid dehydrogenase, an olfactory mucosal cytosolic enzyme localized to sustentacular and Bowman's glandular epithelial cells, was concurrently decreased. By 9 days postdosing, olfactory mucosal lesions had lessened. Results indicate that 3MI transiently injures equine olfactory mucosa without the extensive necrosis, scarring, or metaplasia seen in murine olfactory mucosa or in equine bronchiolar epithelium.

Animals↗
PubMed2001

Effect of adhesion on inducible nitric oxide synthase (iNOS) production in purified human neutrophils.

The production of nitric oxide (NO) within neutrophils is an important element of the innate immune response. We have previously shown that cytokines (IL-1alpha, tumour necrosis factor-alpha and interferon-gamma) induce human neutrophils in buffy coat preparations to produce iNOS. In order to define better the exact requirements for iNOS production within human neutrophils, we have studied the conditions needed for the production of iNOS in purified neutrophils. In contrast to buffy coat preparations, purified neutrophils in suspension did not produce an increase in iNOS following addition of cytokines. However, when purified neutrophils were allowed to adhere to glass surfaces either uncoated or coated with fetal calf serum (FCS), plasma, fibronectin or laminin, there was an increase in the percentage of iNOS-positive cells. The addition of cytokines during adhesion of these cells increased this proportion further. This was most marked for glass alone and FCS-coated glass on which the proportion of iNOS-positive cells increased to 22.7% and 35.5%, respectively, a significant increase compared with cytokine-treated neutrophils in suspension. Neither transmigration through activated endothelial monolayers nor the addition of soluble intercellular adhesion molecule-1 to purified neutrophil suspensions increased the percentage of iNOS-positive cells following cytokine stimulation. Adhesion of neutrophils to surfaces coated with IgG or complement also failed to increase cytokine-induced iNOS production. We conclude that iNOS production in human neutrophils requires not only cytokine stimulation, but also additional stimuli from adhesion to a surface.

Cell Adhesion↗
PubMed2001

Macrophage nitric oxide synthase associates with cortical actin but is not recruited to phagosomes.

Nitric oxide (NO) produced from inducible NO synthase (iNOS) is an important component of host defense against intracellular pathogens. To understand how phagocytes deliver NO to ingested microorganisms while avoiding cytotoxicity, we set out to study the subcellular localization of iNOS within macrophages following phagocytosis. Confocal microscopy of immunostained cells showed that iNOS was located not only diffusely within cytoplasm but also in vesicles, as well as immediately adjacent to the peripheral cell membrane. This peripheral iNOS colocalized with the cortical actin cytoskeleton and was removed by the actin-depolymerizing drug cytochalasin B. Biochemical fractionation of RAW 264 macrophages showed that 32.75% (+/-5.11%; n = 3) of iNOS was present in a particulate fraction, which cosedimented with low-density cellular vesicles. Following phagocytosis of latex beads, zymosan, immunoglobulin G-coated beads, or complement-coated zymosan, submembranous cortical iNOS was not recruited to phagosomes, nor was there any relocalization of intracellular iNOS. Similarly, following phagocytosis of Salmonella enterica serovar Typhimurium there was no recruitment of iNOS to the Salmonella vacuole at any stage after internalization. NO mediated significant killing of intracellular S. enterica serovar Typhimurium in RAW macrophages treated with lipopolysaccharide and gamma interferon; this was evident 4 h after infection. Although not recruited to phagosomes, iNOS association with the submembranous cortical actin cytoskeleton is ideally suited to deliver NO to microbes in contact with the cell surface and may contribute to early killing of ingested Salmonella.

Actins↗
PubMed2001

Increased expression of inducible nitric oxide synthase and cyclo-oxygenase-2 in the airway epithelium of asthmatic subjects and regulation by corticosteroid treatment.

BACKGROUND: Nitric oxide (NO) and prostanoids are mediators of vascular and bronchial tone that are postulated to be involved in asthma. Increased levels of both are found in asthmatic subjects and are synthesised by enzymes that have cytokine inducible forms: inducible NO synthase (iNOS) and cyclo-oxygenase-2 (COX-2), respectively. We hypothesised that the in vivo expression of iNOS and COX-2 in the airways would be increased in asthma, and that these cytokine inducible enzymes may represent targets for regulation by corticosteroid treatment. METHODS: Bronchial biopsy specimens were obtained from three groups of subjects: atopic asthmatics treated with beta(2) agonists alone (n=7), atopic asthmatics additionally receiving regular treatment with corticosteroids (n=8), and non-asthmatic control subjects (n=10). Expression of iNOS and COX-2 mRNA and immunoreactive protein was studied using in situ hybridisation and quantitative immunohistochemistry. RESULTS: Immunoreactivity and the hybridisation signal for iNOS and COX-2 were mainly localised in the airway epithelium. The proportion of epithelium immunostained was significantly greater in the non-steroid treated asthmatic subjects (iNOS 8.6 (1.8)%; COX-2 26.3 (4.6)%) than either the steroid treated asthmatics (iNOS 3.4 (1.0)%, p=0.009; COX-2 13.0 (0.6)%, p=0.0015) or the non-asthmatic controls (iNOS 4.2 (0.9)%, p=0.018; COX-2 11.6 (0.6)%, p=0.0003). Similarly, the hybridisation signal was stronger in the non-steroid treated group of asthmatic subjects than in the other two groups. CONCLUSIONS: These findings highlight the potential role of the airway epithelium both as a contributor to the inflammatory process in asthma and as a target for inhaled corticosteroid treatment in this disease.

Adrenal Cortex Hormones↗
PubMed2000

Neutrophils enhance expression of inducible nitric oxide synthase in human normal but not cystic fibrosis bronchial epithelial cells.

The bronchial epithelium in cystic fibrosis (CF) expresses very low levels of the inducible form of nitric oxide synthase (iNOS). The product of iNOS, nitric oxide (NO), mediates anti-microbial effects and can reduce neutrophil sequestration in the lung. Heavy neutrophilic infiltration of the pulmonary epithelium is a major feature of the end-stage CF lung. This study hypothesized that the system whereby the pulmonary epithelium protects itself against exaggerated neutrophilic infiltration by producing NO is compromised in CF. Human neutrophils were activated by incubation with cytokines, added to monolayers of normal (16HBE14o-) and CF (CFBE41o-) bronchial epithelial cells and co-cultured for up to 72 h. Marked up-regulation of iNOS protein expression was seen in normal bronchial epithelial cells following neutrophil co-culture but the CF cells showed a significantly smaller increase (p<0.001). To determine whether the relative lack of protein was due to a defect in translation, RT-PCR of iNOS mRNA was carried out and a pattern of mRNA expression was seen paralleling that of the protein. The reduced production of NO by CF compared with normal epithelium was shown by the presence of significantly (p<0.001) less accumulated nitrites in medium after co-culture with neutrophils. In summary, this study shows that the normal production of NO by bronchial epithelium in response to contact with neutrophils is lacking in CF. As NO has been shown to oppose neutrophil sequestration, its relative lack in CF may underlie the heavy neutrophilic infiltration that characterizes the disease.

Bronchi↗
PubMed2000

99Tcm-HMPAO leucocyte labelling in orofacial granulomatosis and gastrointestinal Crohn's disease in childhood and early adulthood.

Orofacial granulomatosis is a granulomatous inflammatory disorder, affecting the soft tissues of the face and mouth. The predominant feature is disfiguring lip swelling. Patients with this condition may be exhibiting a Type IV hypersensitivity reaction to dietary or environmental allergens, or these may be the orofacial manifestations of underlying gastrointestinal Crohn's disease. The results of 99Tcm-HMPAO leucocyte labelling of the gastrointestinal tract in 14 patients with orofacial granulomatosis and 15 patients with known gastrointestinal Crohn's disease are presented, indicating that this is a useful and non-invasive screening test for the identification of gastrointestinal Crohn's disease in paediatric and young adult patients presenting with orofacial granulomatosis.

Adolescent↗
PubMed2000

Bioassay for tumor necrosis factors-alpha and -beta.

Tumor necrosis factor (TNF) is a central cytokine in the pathogenesis of septic shock and other inflammatory states. Assay by immunoassay is convenient, but, because of circulating soluble receptors, does not accurately reflect biological activity of the cytokine. This article describes how to perform a bioassay for TNF, using its cytopathic effect on the murine cell line L929. By suitable manipulation, the assay can determine the two different forms of TNF, alpha and beta.

Animals↗
PubMed1999

Energy balance during acute respiratory exacerbations in children with cystic fibrosis.

Acute respiratory exacerbations have been proposed to contribute to the negative energy balance which causes undernutrition in cystic fibrosis. However, no studies have measured their effect on all components of energy balance. The aim of this study was to measure the effect of an acute respiratory exacerbation on energy balance. Fourteen children (six females, eight males, mean+/-SD age 9.9+/-2.4 yrs) were studied when well and during the course of an acute respiratory exacerbation treated with intravenous antimicrobial therapy. The total energy expenditure was measured using the doubly-labelled water method, resting energy expenditure by ventilated hood indirect calorimetry, energy intake by household measures records, and fat malabsorption from measurements of dietary fat intake and faecal fat output. The exacerbation was associated with a significant reduction in energy intake (mean paired difference 47 kJ x kg of body weight(-1) x day(-1), p<0.01). Changes in fat malabsorption and resting energy expenditure were negligible. The absence of significant changes in body weight and composition, together with the trend towards lower total energy expenditure, suggested no marked negative energy balance during the exacerbation. In conclusion, treatment of acute respiratory exacerbation with intravenous antimicrobial therapy represents a relatively minor challenge to energy balance and nutritional status in children with cystic fibrosis.

Acute Disease↗
PubMed1999

13C and H2 breath tests to study extent and site of starch digestion in children with cystic fibrosis.

BACKGROUND: Starch is an important source of energy for children with cystic fibrosis, but little is known about their capacity to digest it. METHODS: A 13C breath test was used to measure starch digestion and oxidation in 16 children with cystic fibrosis (median [range] age, 7.9 [4-15] years; 7 girls, 9 boys) and 5 normal healthy control subjects (median age, 8.3 [7-13] years; 3 girls, 2 boys). A test meal of 13C flour and lactulose was consumed and breath samples were obtained half-hourly thereafter for 6 hours to measure 13C enrichment by isotope ratio mass spectrometry and H2 by electrochemistry. The test was repeated on 10 children with cystic fibrosis when they were taking pancreatic supplements. RESULTS: The median (range) cumulative percentage 13C dose recovery (cPDR), was 35% (18-52%) in control subjects, 18% (9-33%) in children with cystic fibrosis without enzymes, and 29% (22-51%) in those with pancreatic supplements. cPDR differed significantly between healthy control subjects and children with cystic fibrosis without enzymes (p = 0.01) and between children with cystic fibrosis with and without enzymes (p < 0.0001), but there was no difference between control subjects and children with cystic fibrosis taking enzymes (p = 0.5). Eight children with cystic fibrosis had a cPDR within control range, and in six there was a second peak in 13CO2 enrichment coincident with an increase in H2. CONCLUSIONS: Starch digestion and oxidation are diminished in children with cystic fibrosis, but pancreatic enzymes restored them to near normal levels. A second peak in 13CO2 enrichment, suggestive of colonic starch fermentation was absent in healthy children, but present in some children with cystic fibrosis and abolished by pancreatic enzymes.

Adolescent↗
PubMed1999

Adequacy of clinical formulae for estimation of energy requirements in children with cystic fibrosis.

BACKGROUND: Two clinical formulae (CF conference formula and estimation based on 120% of average requirement for energy) have been recommended for the estimation of energy requirements in cystic fibrosis but their accuracy is unknown. AIM: To compare the accuracy of estimates of energy requirement derived from the two formulae. METHODS: Energy requirement, defined as total daily energy expenditure, was measured using the doubly labelled water method in 15 patients (six girls, nine boys; mean (SD) age, 10.0 (2.4) years) who were well and clinically stable. The accuracy of the formulae was assessed using calculation of biases and limits of agreement relative to measured energy requirement. RESULTS: Estimates from the CF conference formula were lower than measured values (mean paired difference, 0.52 MJ/day; 95% confidence interval (CI), -1.10 to 0. 10), but this bias was not significant, and was smaller than that from the alternative formula (mean paired difference, 0.77 MJ/day; 95% CI, -0.20 to 1.74). Limits of agreement relative to measured total daily energy expenditure were narrower for the CF conference formula (-2.72 to 1.68 MJ/day) than for that based on 120% of estimated average requirement (-2.75 to 4.29 MJ/day), but with both formulae errors in estimation at the individual level were large. CONCLUSIONS: The CF conference formula offers improved prediction of energy requirements, but the accuracy of both formulae at the individual level is not sufficiently good for clinical purposes.

Adolescent↗
PubMed1999

The evolution of liver disease in cystic fibrosis.

OBJECTIVES: To describe prospectively the evolution of liver abnormalities in cystic fibrosis (CF), and to assess their impact on nutritional status. STUDY DESIGN: 124 children (61 boys) with CF (median age, 5.4 years; range, 0.1-13.9) were followed longitudinally for a median of four years. Annual clinical examination, biochemistry, and ultrasound assessment were performed. Chrispin-Norman score, anthropometry, and bacterial colonisation of airway secretions were measured at each assessment. RESULTS: At initial assessment, 45% of the patients had no liver abnormalities, 42% had biochemical abnormality, 35% ultrasound abnormality, and 6% had clinical abnormality of the liver. In this cross sectional analysis, abnormal biochemistry was present in 40% of children with ultrasound or clinical abnormalities, but when longitudinal follow up data were analysed, abnormal biochemistry preceded or coincided with abnormal ultrasound or clinical hepatosplenomegaly in three quarters of 53 children developing new abnormalities. Eighty four of 124 children (68%) showed ultrasound or clinical evidence of liver abnormality at some point during the four years of follow up. No association was found between liver disease and nutritional status. CONCLUSIONS: Hepatic abnormality was common in this group of children with CF, was often predicted by intermittent biochemical abnormalities, and was not associated with deterioration in nutritional status.

Adolescent↗
PubMed1999

Cyclooxygenase-2 is widely expressed in atherosclerotic lesions affecting native and transplanted human coronary arteries and colocalizes with inducible nitric oxide synthase and nitrotyrosine particularly in macrophages.

Inflammation appears to have a major role in the development of atherosclerotic lesions affecting native and transplanted coronary arteries. The subsequent risk of plaque rupture and acute ischemic events correlates with the degree of inflammation and may be modified by aspirin, an anti-inflammatory cyclooxygenase inhibitor. Cyclooxygenase-2 (Cox-2) and inducible nitric oxide synthase (iNOS) are involved in the inflammatory response via the rapid and exaggerated production of prostanoids and nitric oxide, both of which may have proatherosclerotic effects. These effects may be mediated by the formation of peroxynitrite in the case of nitric oxide and involve "cross talk" between the two enzyme systems. This study aimed to investigate native and transplant atherosclerosis for the presence and distribution of Cox-2 and iNOS. Immunocytochemical studies were performed on atherosclerotic lesions from patients with native (n=12) and transplant (n=5) coronary disease by using antibodies to Cox-2, iNOS, and nitrotyrosine (an indicator of peroxynitrite production). Control tissue was obtained from unused donor hearts and at the time of autopsy. Cox-2 and iNOS colocalized predominantly in macrophages/foam cells in both types of atherosclerosis. Cox-2 expression was also detected in medial smooth muscle cells and endothelial cells, including those of the vasa vasorum. Nitrotyrosine was found in the same distribution as that of iNOS and was colocalized with Cox-2 in macrophages. Cox-2 and iNOS are coexpressed in native and transplant atherosclerosis, possibly allowing for interaction between the enzymes and suggesting an alternative mechanism for the benefits of aspirin via inhibition of Cox-2 activity.

Animals↗
PubMed1999

Inflammatory bowel disease in Scottish children.

Most children with inflammatory bowel disease (IBD) require specialist care in a tertiary medical centre. The records of 105 children with IBD who presented to the Royal Hospital for Sick Children, Glasgow between 1976 and 1995 were studied retrospectively. Fifty seven children and Crohn's disease (CD) (median age of presentation 7.9 years) and 48 had ulcerative colitis (UC) (median age of presentation 8.7 years). The number with CD doubled in the decade 1986-95 compared to 1975-85. 23% with CD and 13% with UC developed symptoms before the age of five years. Median time to diagnosis from symptom onset was 45.8 weeks for CD and 12.7 weeks for UC. Histological diagnosis was obtained in all children. The mainstay of treatment was aminosalicylates, and few children underwent surgery (CD 26%, UC 10%). Thirty percent with CD and 23% with UC had no relapses in the study period, and only one child with UC died. Growth was poorly recorded. The majority of children with CD and over 50% with UC had a height-for-age Z score below zero.

Body Height↗
PubMed1998

Lack of inducible nitric oxide synthase in bronchial epithelium: a possible mechanism of susceptibility to infection in cystic fibrosis.

Cystic fibrosis (CF) is an inherited disorder associated with severe inflammation and repeated bacterial infection and colonization in the lung. Airway epithelium is involved in defence against bacteria, but this system may be defective in CF. Pro-inflammatory cytokines can stimulate the expression of inducible nitric oxide synthase (iNOS), an enzyme generating nitric oxide, which functions as an important mediator in host defence mechanisms. To understand better the poor resistance to infections in the CF lung, the expression of the iNOS gene was investigated in explanted lungs from patients with cystic fibrosis (n = 13), bronchiectasis (n = 3), emphysema (n = 14), and in normal lungs (n = 8). In addition, bronchial epithelial cell lines were examined to study iNOS gene expression in vitro. Strong immunoreactivity for iNOS was seen in inflammatory cells and bronchial epithelium in all the diseased lungs, except for bronchial epithelium in CF. Quantitative analysis showed a significant reduction in the area of epithelium immunostained in CF [CF 6.8 +/- 1.6 (% +/- SEM); emphysema 18.2 +/- 2.8; normal 9.6 +/- 0.8, P < 0.01], regardless of steroid treatment. These results were supported by in situ hybridization of iNOS mRNA, which showed a pattern of gene expression in CF, emphysema, and normal lung which paralleled that of protein immunoreactivity. Stimulation with cytokines (IL-1 beta, TNF-alpha, and IFN-gamma) increased the expression of iNOS mRNA detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in cultures of normal (16HBE14o-), but not CF (CFBE41o-, with delta F508 CFTR mutation) epithelial cells. Expression of iNOS in inflammatory cells suggests that the gene is normal in CF. Absence of iNOS from bronchial epithelium may be due to low expression of the gene resulting from abnormalities in the signalling system that normally causes induction, such as cytokine receptors, second messengers or transcription factors. The resulting deficiency of the nitric oxide defence system may be relevant to the susceptibility of CF patients to pulmonary bacterial colonization.

Adult↗
PubMed1998

Clinical comparison and performance perspective of three aligning arch wires.

OBJECTIVES: To clinically evaluate three commonly used orthodontic tooth aligning arch wires: 016 x 022 inch active martensitic medium force nickel titanium, 016 x 022 inch graded force active martensitic nickel titanium, and 0.0155 inch multistrand stainless steel. DESIGN: A prospective randomized clinical trial. DATA SOURCE: Measured serial study casts of dental arches for 112 assigned arch wires from 56 consecutive patients. Analysis based on completed records for 98 arch wires and 51 patients. METHOD: A consecutive sample of 56 patients requiring both upper and lower fixed appliance therapy were randomly allocated two different arch wires from a possible three under trial. Good quality impressions were taken of the dental arches at the designated serial stages of alignment (start, T0; 4 weeks, T4; 8 weeks, T8). The resultant casts were measured on a Reflex Microscope to record the change in individual tooth alignment both in three and two dimensions (horizontal plane only). RESULTS: The measurement error was within acceptable limits (range, 0.05 to 0.09 mm) and showed no significant bias. ANOVA statistical models were fitted to the data to adjust for a number of variables. No significant difference in aligning capability (p > 0.05), in either two or three dimensions, was demonstrated between the three arch wires in the trial. CONCLUSION: Heat activated nickel titanium arch wires failed to demonstrate a better performance than the cheaper multistrand stainless steel wires in this randomized clinical trial. The failure to demonstrate in vivo superiority at the clinical level may be due to the confounding effects of large variations in individual metabolic response. Alternatively, it may be that in routine clinical practice NiTi-type wires are not sufficiently deformed to allow their full superelastic properties to come in to play during initial alignment.

Analysis of Variance↗
PubMed1998

Systemic cytokine response to hepatic resections under total vascular exclusion.

OBJECTIVE: To investigate the systemic cytokine response to major liver surgery as the basis for assessing potential new treatments. DESIGN: Open prospective study. SETTING: University hospital, UK. SUBJECTS: Thirteen patients undergoing elective hepatic resections that involved total vascular exclusion of the liver. INTERVENTIONS: Blood samples were taken preoperatively, during the operation, and during the first four postoperative days. Concentrations of endotoxin, interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNFalpha), interleukin-1 (IL-1), and interleukin-6 (IL-6) were measured. RESULTS: Endotoxin concentrations were raised in 3/13 patients before operation and in 6 patients during the postoperative period. TNFalpha concentrations were undetectable. IFN-gamma and IL-1 responses followed a low and inconclusive pattern. IL-6 was significantly increased from 6 hours after operation to the third postoperative day, peaking at 699 (+/-277) pg/ml at 24 hours (p < 0.01). The two patients who died had the highest postoperative concentrations of IL-6. CONCLUSIONS: There is a pronounced systemic response to hepatic resection under total vascular exclusion that is reflected by the increase in IL-6 concentration and correlates with the operative blood loss and postoperative outcome. This might be used as an indicator of the response to specific treatments in this type of surgery. Treatments that minimise the IL-6 response to major hepatic resection may be of value.

APACHE↗