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Biomedical subjects

M Evans

Publications and source records attributed to M Evans.

At least 19 recordsLinked to original sources
PubMed2006

Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes.

UNLABELLED: Type 2 diabetes (T2DM) is associated with chronic low-grade inflammation. Adipose tissue (AT) may represent an important site of inflammation. 3T3-L1 studies have demonstrated that lipopolysaccharide (LPS) activates toll-like receptors (TLRs) to cause inflammation. For this study, we 1) examined activation of TLRs and adipocytokines by LPS in human abdominal subcutaneous (AbdSc) adipocytes, 2) examined blockade of NF-kappaB in human AbdSc adipocytes, 3) examined the innate immune pathway in AbdSc AT from lean, obese, and T2DM subjects, and 4) examined the association of circulating LPS in T2DM subjects. The findings showed that LPS increased TLR-2 protein expression twofold (P<0.05). Treatment of AbdSc adipocytes with LPS caused a significant increase in TNF-alpha and IL-6 secretion (IL-6, CONTROL: 2.7+/-0.5 vs. LPS: 4.8+/-0.3 ng/ml; P<0.001; TNF-alpha, CONTROL: 1.0+/-0.83 vs. LPS: 32.8+/-6.23 pg/ml; P<0.001). NF-kappaB inhibitor reduced IL-6 in AbdSc adipocytes ( CONTROL: 2.7+/-0.5 vs. NF-kappaB inhibitor: 2.1+/-0.4 ng/ml; P<0.001). AbdSc AT protein expression for TLR-2, MyD88, TRAF6, and NF-kappaB was increased in T2DM patients (P<0.05), and TLR-2, TRAF-6, and NF-kappaB were increased in LPS-treated adipocytes (P<0.05). Circulating LPS was 76% higher in T2DM subjects compared with matched controls. LPS correlated with insulin in controls (r=0.678, P<0.0001). Rosiglitazone (RSG) significantly reduced both fasting serum insulin levels (reduced by 51%, P=0.0395) and serum LPS (reduced by 35%, P=0.0139) in a subgroup of previously untreated T2DM patients. In summary, our results suggest that T2DM is associated with increased endotoxemia, with AT able to initiate an innate immune response. Thus, increased adiposity may increase proinflammatory cytokines and therefore contribute to the pathogenic risk of T2DM.

Adipocytes, White↗
PubMed2006

Basal ganglia lesions after MPTP administration in rhesus monkeys.

In monkeys, intracarotid infusion of a single low dose of MPTP reliably induces a hemiparkinsonian syndrome that is stable over time. This model has been widely used to assess novel anti-parkinsonian therapies. Here, we report the exceptional finding of severe necrotic lesions that were observed in the basal ganglia (but not in the substantia nigra) of monkeys that received a single intracarotid injection of MPTP followed by gene therapy treatments. Although extensive unilateral dopaminergic nigrostriatal loss was found in all the animals, partial behavioral recovery was observed in the subjects that presented pallidal necrotic lesions. This report discusses possible causes and effects of the necrotic lesions and their locations and the value of the intracarotid MPTP model. Testing novel therapies in monkey models has become an essential step before clinical trials. These results indicate that evaluation of any treatment should consider possible confounding factors that may affect the results.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2006

Effects of a thyroid-stimulating human monoclonal autoantibody (M22) on functional activity of LH and FSH receptors.

OBJECTIVE: The glycoprotein hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyrotropin (TSH) show low-level cross-reactivity between their respective receptors (R). Patient serum autoantibodies to the thyrotropin receptor (TSHR) do not appear to cross-react with the luteinizing hormone receptor (LHR) or follicle-stimulating hormone receptor (FSHR), although the concentrations of autoantibody with which it is feasible to carry out experiments of this type are limited. Consequently, we have studied the effects of high doses of the thyroid-stimulating human monoclonal autoantibody (M22) on the LHR and FSHR. DESIGN: Chinese Hamster ovary (CHO) cells stably expressing the TSHR, LHR, and FSHR and purified M22 IgG preparations were used in the study. METHODS: CHO-TSHR, CHO-LHR, and CHO-FSHR cells were incubated with bovine TSH (0.1-25mU/mL), human recombinant chorionic gonadotropin (hCG; 0.5-10mU/mL) or human recombinant FSH (100-5000mU/mL) or with M22 IgG (0.001-5.0 microg/mL), and the extracellular cyclic AMP was measured by radioimmunoassay. RESULTS: Cyclic AMP levels increased in a dose-dependent manner after incubation of CHO-TSHR cells with TSH or M22 IgG, and on a molar basis the effects of TSH and M22 were similar. Cyclic AMP stimulation was not detectable in CHO-LHR and CHO-FSHR cells after incubation with M22 IgG, whereas incubation with hCG or FSH, respectively, caused dose-dependent cyclic AMP stimulation. On a molar basis, concentrations of M22 IgG approximately 100x those of FSH causing clear stimulation were ineffective with CHO-FSHR cells. Similarly, molar concentration of M22 IgG 20,000x those of hCG causing clear stimulation had no effect on CHO-LHR cells. CONCLUSIONS: This study shows that at relatively high concentrations, M22 IgG is unable to stimulate cyclic AMP levels in CHO-LHR or CHO-FSHR cells, suggesting that TSHR autoantibodies have greater specificity for the TSHR than TSH itself.

Animals↗
PubMed2006

Accurate skin dose measurements using radiochromic film in clinical applications.

Megavoltage x-ray beams exhibit the well-known phenomena of dose buildup within the first few millimeters of the incident phantom surface, or the skin. Results of the surface dose measurements, however, depend vastly on the measurement technique employed. Our goal in this study was to determine a correction procedure in order to obtain an accurate skin dose estimate at the clinically relevant depth based on radiochromic film measurements. To illustrate this correction, we have used as a reference point a depth of 70 micron. We used the new GAFCHROMIC dosimetry films (HS, XR-T, and EBT) that have effective points of measurement at depths slightly larger than 70 micron. In addition to films, we also used an Attix parallel-plate chamber and a home-built extrapolation chamber to cover tissue-equivalent depths in the range from 4 micron to 1 mm of water-equivalent depth. Our measurements suggest that within the first millimeter of the skin region, the PDD for a 6 MV photon beam and field size of 10 x 10 cm2 increases from 14% to 43%. For the three GAFCHROMIC dosimetry film models, the 6 MV beam entrance skin dose measurement corrections due to their effective point of measurement are as follows: 15% for the EBT, 15% for the HS, and 16% for the XR-T model GAFCHROMIC films. The correction factors for the exit skin dose due to the build-down region are negligible. There is a small field size dependence for the entrance skin dose correction factor when using the EBT GAFCHROMIC film model. Finally, a procedure that uses EBT model GAFCHROMIC film for an accurate measurement of the skin dose in a parallel-opposed pair 6 MV photon beam arrangement is described.

Computer Simulation↗
PubMed2005

Upper limits on a stochastic background of gravitational waves.

The Laser Interferometer Gravitational-Wave Observatory has performed a third science run with much improved sensitivities of all three interferometers. We present an analysis of approximately 200 hours of data acquired during this run, used to search for a stochastic background of gravitational radiation. We place upper bounds on the energy density stored as gravitational radiation for three different spectral power laws. For the flat spectrum, our limit of omega0 < 8.4 x 10(-4) in the 69-156 Hz band is approximately 10(5) times lower than the previous result in this frequency range.

Journal Article↗
PubMed2005

Limits on gravitational-wave emission from selected pulsars using LIGO data.

We place direct upper limits on the amplitude of gravitational waves from 28 isolated radio pulsars by a coherent multidetector analysis of the data collected during the second science run of the LIGO interferometric detectors. These are the first direct upper limits for 26 of the 28 pulsars. We use coordinated radio observations for the first time to build radio-guided phase templates for the expected gravitational-wave signals. The unprecedented sensitivity of the detectors allows us to set strain upper limits as low as a few times 10(-24). These strain limits translate into limits on the equatorial ellipticities of the pulsars, which are smaller than 10(-5) for the four closest pulsars.

Journal Article↗
PubMed2005

Prenatal diagnosis of echogenic lung: evolution and outcome.

OBJECTIVES: Despite the feasibility of detecting lung lesions by antenatal ultrasound, there are problems in correlating the prenatal diagnosis with the final histology and in predicting the outcome. In order to better describe these factors, we reviewed the outcome of fetuses that had been diagnosed with echogenic lung in a referral fetal medicine unit. METHODS: We searched the database of a tertiary fetal medicine unit for all cases of fetal echogenic lung seen since 1994 and studied the maternal and neonatal records found. RESULTS: There were 48 cases of echogenic lung diagnosed at a median gestational age of 21 (range, 19-29) weeks, including 43 (90%) cases of congenital cystic adenomatoid malformation (CCAM) and 5 (10%) of pulmonary sequestration (PS). The evolution of the fetal abnormality after diagnosis was: in 22 (45.8%) cases the lesion disappeared; in 17 (35.5%) cases the lesion remained stable and six (12.5%) cases became severe. Three (6%) women underwent termination of pregnancy. The lesions were equally distributed between the two sides of the thorax. Mediastinal shift was associated with a threefold increase in the possibility of clinical deterioration (17% vs. 5%), and the disappearance of the lesion was twice as likely to occur when the lesion was classified as microcystic as when it was macrocystic (67% vs. 36%). Features of hydrops were found in 9 (21%) fetuses and in six (13%) cases progressed and resulted in intrauterine or neonatal death. Sixty-four percent of cases with lesions that disappeared during the pregnancy had an abnormal computed tomography (CT) scan, and the prenatal diagnosis correlated with histology in 36% of these cases. Of the cases in which the lesions remained stable, 70.5% had an abnormal CT scan and the prenatal diagnosis correlated with the histology in 67% of the cases. CONCLUSIONS: Prenatally diagnosed echogenic lung has a good prognosis in the absence of hydrops. The ability to correctly assess echogenic lung lesions and the need for surgery by prenatal ultrasound is limited.

Cystic Adenomatoid Malformation of Lung, Congenita↗
PubMed2005

Isolation and characterisation of a human monoclonal autoantibody to the islet cell autoantigen IA-2.

A hybridoma secreting a human monoclonal autoantibody to the islet cell autoantigen IA-2 was prepared from peripheral lymphocytes of a patient with type 1 diabetes and Graves' disease using EBV infection followed by fusion with a mouse/human hybrid cell line. The monoclonal antibody (M13) is an IgG1/kappa and in an immunofluorescence test M13 at 1 microg/mL showed islet cell antibody reactivity equivalent to 40 JDF units. M13 IgG bound (35)S-labelled IA-2 (26% at 100 microg/mL) and (125)I-labelled IA-2 (34% at 100 microg/mL) in an immunoprecipitation assay and reacted well with IA-2 in western blotting analysis. Amino acids 777-808 in the PTP domain of IA-2 were found to be important for M13 binding in an analysis using modified (35)S-labelled IA-2 proteins. M13 V region genes were from VH1-3, D3-22, JH4b, VKI DPK8/Vd+ and JK3 genes and showed a high replacement/silent mutation ratio for both the heavy (11.0) and the light (6.0) chain genes. Mouse monoclonal antibodies (mMAbs) reactive with at least three different epitopes within IA-2 aa 604-686 corresponding to the juxtamembrane domain were also obtained. F(ab')(2) or Fab from the mMAbs inhibited serum IA-2 autoantibody binding to IA-2 in 20/22 diabetic sera whereas M13 F(ab')(2) caused inhibition in only 6/22 sera. M13 is representative of some patient serum IA-2 autoantibodies and as such provides a useful tool to study autoimmune responses to IA-2.

Animals↗
PubMed2005

Post traumatic distress symptoms following spinal cord injury: a comparative review of European samples.

OBJECTIVE: To highlight any cross-cultural differences in the prevalence of post traumatic distress (PTD), and the type of coping strategies implemented following spinal cord injury (SCI). DESIGN: Cross-sectional questionnaire. SETTING: A spinal cord rehabilitation unit in the UK, and six Swiss and German (CH/DE) spinal injury centres. METHOD: A total of 85 SCI individuals in the UK, and 71 in CH/DE were evaluated on levels of PTD using the Impact of Event Scale (IES), and depressive symptomatology using the Beck Depression Inventory or the Berne Questionnaire of Well-Being at up to 6 months postinjury. In addition, the coping strategies utilised by the two samples were assessed using the COPE measure. RESULTS: No significant difference between the two samples was noted with regard to levels of PTD determined by the total score on the IES, although there was a tendency for a higher rate in the UK. Approximately 20 and 10% of both samples scored above the clinical cutoff on the IES subscales of intrusion and avoidance, respectively. No significant difference was found to exist between the rate of PTD in the SCI CH/DE sample and the able-bodied sample in Switzerland. A lower prevalence of depression was noted in the CH/DE sample. The CH/DE sample scored higher on the use of positive reinterpretation and growth, suppression of competing activities, active and restraint coping, whereas the UK sample scored higher on the use of humour as a coping strategy. Overall, denial, focusing on and venting of emotions, mental disengagement and suppression of competing activities were associated with PTD. CONCLUSION: No cross-cultural differences in the level of PTD seem apparent between the UK and CH/DE populations. Future research should focus on determining what protects individuals from developing PTD following SCI.

Adolescent↗
PubMed2005

A novel technique of concurrent esophagoscopy and transgastrostomy gastroscopy to dilate a completely obstructed distal esophageal stricture in a child following fundoplication.

We report a successful dilation of a completely obstructed distal esophageal stricture in a 4-year-old boy with combined immune deficiency syndrome, at 2 and half years after fundoplication and gastrostomy tube insertion. Barium studies and esophagoscopy had revealed complete obstruction of the lower esophagus. Transgastrostomy gastroscopy demonstrated a pinhole lumen through the fundoplication wrap; a guide wire was passed into the esophagus; and the stricture was dilated with Savary dilators. We presumed that the stricture was secondary to chronic esophagitis. The stricture was identified and successfully dilated using a novel technique of concurrent esophagoscopy and transgastrostomy gastroscopy.

Child, Preschool↗
PubMed2005

Characteristics of a monoclonal antibody to the thyrotropin receptor that acts as a powerful thyroid-stimulating autoantibody antagonist.

Analysis of nine mouse monoclonal antibodies (mAbs) to the thyrotropin receptor (TSHR) with TSH antagonist activity showed that only one of the mAbs (RSR B2) was an effective antagonist of the human thyroid stimulating autoantibody M22. Crystals of B2 Fab were analyzed by x-ray diffraction and a crystal structure at 3.3 A resolution was obtained. The surface charge and topography of the B2 antigen binding site were markedly different from those of the thyroid-stimulating mAb M22 and these differences might contribute to the different properties of the two mAbs. B2 (but not other mouse TSHR-specific mAbs) was also an effective antagonist of thyroid stimulating autoantibody activity in 14 of 14 different sera from patients with Graves' disease. 125I-labeled B2 bound to the TSHR with high affinity (2 x 10(10) L/mol) and patient serum TSHR autoantibodies inhibited labeled B2 binding to the receptor in a similar way to inhibition of labeled TSH binding (r = 0.75; n = 20). Furthermore, labeled B2 binding was inhibited by patient serum TSHR autoantibodies with TSH antagonist activity and also by mouse and human thyroid stimulating mAbs. Overall, mAb B2 is a powerful antagonist of thyroid stimulating autoantibodies (and TSH) thus resembling closely patient serum TSH antagonist TSHR autoantibodies. Furthermore, B2 might have potentially important in vivo applications when tissues containing the TSHR (including those in the orbit) need to be made unresponsive to stimulating autoantibodies.

Animals↗
PubMed2005

In vitro efficacy of a whitening toothpaste containing calcium carbonate and perlite.

OBJECTIVES: The studies described in this paper aimed to assess the stain removal efficacy, fluoride efficacy and abrasivity to enamel and dentine of a new whitening toothpaste containing calcium carbonate and perlite, using appropriate in vitro models. METHODS: Stain removal efficacy was assessed using the pellicle cleaning ratio (PCR) method. Fluoride efficacy was assessed using remineralisation, demineralisation and fluoride-uptake methods. Abrasivity was assessed using an enamel and dentine wear method. RESULTS: The results showed that the new whitening toothpaste was able to remove extrinsic tooth stain more effectively than three commercially available toothpaste formulations. The fluoride efficacy was superior to a non-fluoridated control and was not significantly different to a clinically tested fluoride-containing toothpaste. The abrasivity data showed that the calcium carbonate/perlite toothpaste is no more abrasive to enamel or dentine than two other commercially available whitening toothpastes. CONCLUSIONS: The studies show that the new whitening toothpaste is effective in extrinsic stain removal, has an efficacious fluoride source and does not have an undue degree of abrasivity to enamel or dentine compared to other relevant commercially available products.

Aluminum Oxide↗
PubMed2005

Efficacy of the combination rifampin-streptomycin in preventing growth of Mycobacterium ulcerans in early lesions of Buruli ulcer in humans.

Mycobacterium ulcerans disease is common in some humid tropical areas, particularly in parts of West Africa, and current management is by surgical excision of skin lesions ranging from early nodules to extensive ulcers (Buruli ulcer). Antibiotic therapy would be more accessible to patients in areas of Buruli ulcer endemicity. We report a study of the efficacy of antibiotics in converting early lesions (nodules and plaques) from culture positive to culture negative. Lesions were excised either immediately or after treatment with rifampin orally at 10 mg/kg of body weight and streptomycin intramuscularly at 15 mg/kg of body weight daily for 2, 4, 8, or 12 weeks and examined by quantitative bacterial culture, PCR, and histopathology for M. ulcerans. Lesions were measured during treatment. Five lesions excised without antibiotic treatment and five lesions treated with antibiotics for 2 weeks were culture positive, whereas three lesions treated for 4 weeks, five treated for 8 weeks, and three treated for 12 weeks were culture negative. No lesions became enlarged during antibiotic treatment, and most became smaller. Treatment with rifampin and streptomycin for 4 weeks or more inhibited growth of M. ulcerans in human tissue, and it provides a basis for proceeding to a trial of antibiotic therapy as an alternative to surgery for early M. ulcerans disease.

Adolescent↗
PubMed2005

The effects of atorvastatin in experimental autoimmune uveitis.

AIM: To investigate the effect of atorvastatin (Lipitor), a commonly used drug for dyslipidaemia in experimental autoimmune uveitis (EAU). METHODS: 48 B10-RIII mice were immunised with human interphotoreceptor retinoid binding protein (IRBP) peptide p161-180. They were divided into three groups of 16 each and treated orally once daily for 14 days; group one received phosphate buffered saline (control group), group two received 1 mg/kg of atorvastatin (low dose group), and group three received 10 mg/kg (high dose). On day 14 lymph nodes, spleens, and right eyes were harvested. RNA was extracted from lymph nodes for RNase protection assay (RPA) to determine proinflammatory (IL-1 alpha and IL-1 beta), Th1 (TNF-alpha, IL-2, IL-12), and Th2 (IL-4, IL-5, and IL-10) cytokine levels. Protein was extracted from spleens for western blot to detect the expression of phosphorylated signal transducer and activator of transcription (STAT) 4 and STAT6. The severity of inflammation in enucleated eyes was graded by a masked observer. Paired t test was performed for the mean difference in histological scoring between treated groups and the immunised control group. RESULTS: Surprisingly, atorvastatin did not modulate the immune response. The proinflammatory cytokines, IL-1 alpha and IL-1 beta, and Th1 cytokines, TNF-alpha and IL-2, were upregulated equally in control and atorvastatin treated groups. IL-12 and Th2 cytokines were not upregulated in all three groups. Western blot analysis showed high levels of phosphorylated STAT4, but not STAT6 protein in the control and atorvastatin treated groups. Mean differences in histological scoring between treated groups and the immunised control group were not statistically significant. CONCLUSIONS: Atorvastatin treatment had no effect on Th1 and Th2 cytokine transcription. Although histological grading suggested mildly decreased inflammation in the high dose treated group, the equivalence of cytokine expression in all groups suggests that the statins may not modulate IRBP induced uveoretinitis.

Animals↗
PubMed2005

Influence of body weight, age, and weight gain on fertility and prolificacy in four breeds of ewe lambs.

Breeding ewes to lamb at 1 yr of age can improve profitability for some production systems. The first objective of this study was to evaluate the effect of age and weight at breeding and total postweaning weight gain on reproductive performance of ewe lambs. The second objective was to compare the effects of weight and age variables in four major sheep breeds (Columbia, Polypay, Rambouillet, and Targhee). Weights, ages, and the binary traits of fertility (pregnant or nonpregnant) and prolificacy (one lamb born vs. two or more) were collected on 2,055 ewe lambs at the U.S. Sheep Experiment Station, Dubois, ID, from 1984 through 1988. The effects of age and weight at breeding and total weight gain from weaning to breeding on fertility and prolificacy were analyzed with a logit model in a maximum likelihood analyses. Differences (P < 0.001) among breeds for fertility were identified, with a 93% fertility rate for Polypay ewe lambs compared with lower fertility rates in Columbia, Targhee, and Rambouillet ewe lambs (50, 60, and 75%, respectively). The percentage of multiple births (prolificacy rate) also was higher (P < 0.001) in the Polypay (47%) than in Columbia, Targhee, and Rambouillet breeds (1, 13, and 14%, respectively). Averaged across breeds, weight at breeding had a positive effect on fertility and prolificacy (P < 0.001), whereas total weight gain from weaning to breeding had a positive effect only on fertility (P < 0.027). In separate analyses for each breed, increasing age (P < 0.001) and weight at breeding (P < 0.001) increased the probability of pregnancy in Rambouillet ewe lambs. The probability of pregnancy for Targhee ewe lambs increased (P < 0.005) with weight at breeding. Increasing weight at breeding increased (P < 0.004) the probability of multiple births in all breeds. Increasing total postweaning weight gain increased (P < 0.007) the probabilities of multiple births in Rambouillet and Targhee ewe lambs. In conclusion, Polypay ewe lambs were superior in fertility and prolificacy to Columbia, Rambouillet, and Targhee under Western range conditions. Improved reproductive performance of Columbia, Rambouillet, and Targhee ewe lambs may be achieved by increasing age and weight at breeding and postweaning gain.

Age Factors↗