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21.
Inhibition of allergic airways inflammation and airway hyperresponsiveness in mice by dexamethasone: role of eosinophils,IL-5, eotaxin,and IL-13 总被引:4,自引:0,他引:4
Eum SY Maghni K Hamid Q Eidelman DH Campbell H Isogai S Martin JG 《The Journal of allergy and clinical immunology》2003,111(5):1049-1061
BACKGROUND: Glucocorticoids inhibit allergen-induced airway eosinophilia and airway hyperresponsiveness (AHR). Whether glucocorticoids mediate their effects on AHR by inhibiting eotaxin and IL-5, 2 of the principal mediators of eosinophilia, or through IL-13, an important mediator of AHR, has not been established. OBJECTIVE: We sought to investigate the effects of glucocorticoids on airway eosinophilia and the expression of IL-5, eotaxin, and IL-13 in relation to the induction of AHR in a murine model of allergic asthma. METHODS: Dexamethasone (4 mg/kg) and mAbs against eotaxin (80 micro g/kg) and IL-5 (100 micro g/kg) singly and in combination were administered to immunized mice before antigen challenge. Airway responsiveness to methacholine was measured in anesthetized and mechanically ventilated animals. Eotaxin, IL-5, and IL-13 in bronchoalveolar lavage fluid (BALF), lung homogenates, or both were measured by means of ELISA. RESULTS: A single antigen challenge induced AHR that lasted at least 10 days. Eotaxin protein and mRNA levels increased in lung tissue but not in BALF after challenge. IL-5 protein and mRNA levels increased both in BALF and in lung tissue. Dexamethasone reduced airway eosinophilia, AHR, and protein and mRNA for eotaxin and IL-5. Anti-murine eotaxin and anti-IL-5 antibodies alone and in combination reduced the ovalbumin-induced airway eosinophilia significantly but failed to inhibit AHR. Both dexa-methasone and anti-IL-5/anti-eotaxin inhibited the increases in lung IL-13 levels after ovalbumin challenge to a similar extent. CONCLUSION: These findings suggest that the inhibition of AHR by the glucocorticoid dexamethasone does not appear to be explained by effects on eosinophilia, eotaxin, IL-5, or IL-13. 相似文献
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23.
Human papillomavirus infection in Egyptian esophageal carcinoma: correlation with p53, p21, mdm2, C-erbB2 and impact on survival 总被引:1,自引:0,他引:1
The etiological role of human papillomavirus (HPV) in esophageal carcinoma (EC) in relation to p53, mdm2, p21(waf), c-erbB2 and the overall survival (OS) rate was investigated. Tumor and normal tissues from 50 EC were evaluated by polymerase chain reaction and InnoLiPA for HPV. Single strand conformation polymorphism/sequencing were used to detect p53 gene mutations. Immunohistochemistry was performed to determine p53, mdm2, p21(waf)and c-erbB2 expression. Human papillomavirus was detected in 54% of tumors and in 24% of normal tissues. p53, mdm2 and c-erbB2 overexpression was detected in 68%, 70% and 60% of tumors and in 14%, 16% and 10% of normal samples, whereas loss of p21(waf) was evident in 64% of tumors. p53 mutations were detected in 20% of cases. Exon 8 and 5 showed the highest mutation rate (40% each), followed by exons 6 and 7 (10% each). There was a significant correlation between HPV and p53, mdm2, c-erbB2 overexpression. The OS was significantly associated with overexpression of p53 and loss of p21(waf). Human papillomavirus infection is frequent in Egyptian EC. Both p53-dependent and p53-independent pathways seem to be involved in HPV-associated EC. mdm2 and c-erbB2 are possible targets for HPV in the p53-independent pathway. However, only advanced stage and aberrant expression of p53 and p21(waf) are independent prognostic markers. 相似文献
24.
Variations in Helicobacter pylori lipopolysaccharide to evade the innate immune component surfactant protein D 总被引:2,自引:0,他引:2
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Khamri W Moran AP Worku ML Karim QN Walker MM Annuk H Ferris JA Appelmelk BJ Eggleton P Reid KB Thursz MR 《Infection and immunity》2005,73(11):7677-7686
Helicobacter pylori is a common and persistent human pathogen of the gastric mucosa. Surfactant protein D (SP-D), a component of innate immunity, is expressed in the human gastric mucosa and is capable of aggregating H. pylori. Wide variation in the SP-D binding affinity to H. pylori has been observed in clinical isolates and laboratory-adapted strains. The aim of this study was to reveal potential mechanisms responsible for evading SP-D binding and establishing persistent infection. An escape variant, J178V, was generated in vitro, and the lipopolysaccharide (LPS) structure of the variant was compared to that of the parental strain, J178. The genetic basis for structural variation was explored by sequencing LPS biosynthesis genes. SP-D binding to clinical isolates was demonstrated by fluorescence-activated cell sorter analyses. Here, we show that H. pylori evades SP-D binding through phase variation in lipopolysaccharide. This phenomenon is linked to changes in the fucosylation of the O chain, which was concomitant with slipped-strand mispairing in a poly(C) tract of the fucosyltransferase A (fucT1) gene. SP-D binding organisms are predominant in mucus in vivo (P = 0.02), suggesting that SP-D facilitates physical elimination. Phase variation to evade SP-D contributes to the persistence of this common gastric pathogen. 相似文献
25.
26.
Evaluation of cleaving agents other than trypsin in direct agglutination test for further improving diagnosis of visceral leishmaniasis. 总被引:3,自引:0,他引:3
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A el Harith S Chowdhury A al-Masum S Semio-Santos E Karim S el-Safi I Haque 《Journal of clinical microbiology》1995,33(8):1984-1988
Trypsin treatment of Leishmania promastigote antigen has proved to be indispensible in the direct agglutination test (DAT) for the diagnosis of visceral leishmaniasis (VL) and canine visceral leishmaniasis (CVL). In the present study four antigen batches were prepared with pronase (400 micrograms/ml), lipase (0.45% [wt/vol]), pancreatin (0.3% [wt/vol]), or 2-mercaptoethanol (2-ME) (1.2% [vol/vol]) at a ratio of 20:1 versus promastigote packed cell volume or a density of 10(8)/ml. Batches prepared in this way performed satisfactorily when compared with the performance of the initial trypsinated antigen. Even higher was the sensitivity and specificity of the 2-ME-processed antigen, scoring a minimum DAT titer of 1:102,400 in the VL and CVL group and a maximum of 1:400 in the negative control group. Corresponding titers ranging from 1:6,400 to 1:12,800 and 1:800 to 1:1,600 were obtained with the antigen variants processed with pronase, lipase, pancreatin, or trypsin. By combining the use of indigenous Leishmania donovani subspecies from Sudan, Bangladesh, or Morocco and incorporating 2-ME instead of trypsin in the antigen processing step, a threefold increase in titer was attained in sera from the respective areas where VL is endemic. 2-ME-processed antigen suspensions maintained stability at 4 degrees C for up to 9 months, as evidenced by the absence of autoagglutination and the reproducibility of DAT readings with standard sera. The specificity of DAT was further improved by supplementation of the sample diluent with 0.03 M urea and incubation of the test plates at 37 degrees C for 1 h.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
27.
A-kinase anchoring proteins (AKAPs) constitute a family of scaffolding proteins that bind the regulatory subunits of protein kinase A (PKA). AKAP binding to PKA regulates the phosphorylation of various proteins, some of which have been implicated in synaptic plasticity and memory consolidation. Here we show that the regulatory subunits of PKA are colocalized with AKAP150 (an AKAP isoform that is expressed in the brain) in the lateral amygdala (LA) and that infusion to the LA of the peptide St-Ht31, which blocks PKA anchoring onto AKAPs, impairs memory consolidation of auditory fear conditioning. 相似文献
28.
Determinants of the effect of estrogen on the progression of subclinical atherosclerosis: Estrogen in the Prevention of Atherosclerosis Trial 总被引:1,自引:0,他引:1
Karim R Mack WJ Lobo RA Hwang J Liu CR Liu CH Sevanian A Hodis HN 《Menopause (New York, N.Y.)》2005,12(4):366-373
OBJECTIVE: To determine the extent to which the estrogen-induced changes in lipids and markers of carbohydrate metabolism explain the beneficial effect of estrogen therapy on the progression of carotid artery intima-media thickness (IMT) in postmenopausal women. DESIGN: A randomized, double-blind, placebo-controlled, single-center trial enrolling 222 postmenopausal women 45 years and older without cardiovascular disease and with low-density lipoprotein (LDL) cholesterol levels of 3.37 mmol/L or greater (> or = 130 mg/dL). Intervention was unopposed micronized 17beta-estradiol versus placebo. Measurements were made using high-resolution B-mode ultrasonography to measure carotid artery IMT at baseline and every 6 months on-trial. RESULTS: Progression of carotid IMT was inversely related to on-trial high-density lipoprotein (HDL) cholesterol (P = 0.04) and was directly related to on-trial LDL-cholesterol (P = 0.005). Compared with placebo, women randomized to estradiol showed a higher mean on-trial HDL-cholesterol level and a lower mean on-trial LDL-cholesterol level. In contrast, fasting glucose, insulin, and hemoglobin A1C were lowered and insulin sensitivity increased with estradiol therapy, but the changes were not related to carotid IMT progression. On-trial HDL-cholesterol and LDL-cholesterol were significant independent determinants of carotid IMT progression, jointly explaining 30% of the treatment effect of unopposed estrogen on the progression of carotid IMT. CONCLUSION: Unopposed 17beta-estradiol reduced carotid IMT progression in postmenopausal women in part by increasing HDL-cholesterol and decreasing LDL-cholesterol. Although women randomized to estradiol showed improvement in all the markers of carbohydrate metabolism, these factors did not play a significant role in carotid IMT progression. 相似文献
29.
Combination of reverse transcriptase PCR analysis and immunoglobulin M detection on filter paper blood samples allows diagnostic and epidemiological studies of measles
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30.
The growth in length and weight of 91 poor urban Bangladeshi infants was monitored at monthly intervals from birth to 1 year. At birth 18%, 22% and 8% were below -2.00 standard deviations of the National Center for Health Statistics (NCHS) height-for-age, weight-for-age and weight-for-height, respectively and at 1 year the percentages were 40%, 40% and 7%. Infant weights over the first 6 months associated positively with both mother's BMI and percentage body fat. Higher mean infant weights from 6 to 12 months were associated with both higher educational status of the mother and monthly family income and the latter two variables provided the best model for predicting weight velocity from birth to 12 months. Internal Z-scores, corrected for day of measurement, provided clear evidence of catch-up/catch-down over the first 6 months with heavier and longer babies at birth showing catch-down while lighter and shorter babies demonstrated catch-up. Infants' weights were almost three times more variable than lengths. Monthly incremental variability of both infant weight and length increased sharply from 6 to 12 months with weight showing significantly more variability. The correlations of birth weight and length with subsequent distances and monthly increment revealed that the first 6 months were dominated by catch-up and catch-down but during the latter half of the year the growth phenomena were influenced mainly by earlier intra-uterine or genetic effects. 相似文献