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1.

Background

Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.

Methods

Resistin levels were measured in plasma and sputum from three retrospective CF cohorts spanning a wide range of disease. We also assessed the ability of neutrophils to secrete resistin upon activation in vitro. Finally, we constructed a multivariate model assessing the relationship between resistin levels and lung function.

Results

Plasma resistin levels were only marginally higher in CF than in healthy control subjects. By contrast, sputum resistin levels were very high in CF, reaching 50–100 fold higher levels than in plasma. Among CF patients, higher plasma resistin levels were associated with allergic bronchopulmonary aspergillosis, and higher sputum resistin levels were associated with CF-related diabetes. Mechanistically, in vitro release of neutrophil primary granules was concomitant with resistin secretion. Overall, sputum resistin levels were negatively correlated with CF lung function, independently of other variables (age, sex, and genotype).

Conclusions

Our data establish relationships between resistin levels in the plasma and sputum of CF patients that correlate with disease status, and identify resistin as a novel mechanistic link between neutrophilic inflammation and lung disease in CF.  相似文献   
2.
3.
We previously reported poorer survival among non-Hispanic blacks and Hispanics with idiopathic pulmonary fibrosis (IPF) compared to non-Hispanic whites at our center. In the current study, we hypothesized that these disparities would exist in a nationwide cohort of wait-listed patients with IPF. We performed a retrospective cohort study of 2635 patients with IPF listed for lung transplantation between 1995 and 2003 at 94 transplant centers in the United States. The age-adjusted mortality rate was higher among non-Hispanic blacks [hazard ratio (HR) = 1.24, 95% confidence interval (CI) 1.06-1.45, p = 0.009] and Hispanics (HR = 1.29, 95% CI 1.06-1.56, p = 0.01) compared to non-Hispanic whites. These findings persisted after adjustment for transplantation, medical comorbidities and socioeconomic status. Worse lung function at the time of listing appeared to explain some of these differences (HR for non-Hispanic blacks after adjustment for forced vital capacity percent predicted = 1.16, 95% CI 0.98-1.36, p = 0.09; HR for Hispanics = 1.21, 95% CI 0.99-1.48, p = 0.056). In summary, black and Hispanic patients with IPF have worse survival than whites after listing for lung transplant.  相似文献   
4.
目的构建pCool—GST—ICAD/CAD的表达载体,并存大肠杆菌BL21(DE3)中表达具有生物学活性的CAD核酸酶?方法用PCR扩增CAD基因,将扩增产物克隆入pCool—GST—ICAD载体中构建出pCool—GST—ICAD/CAD表达载体。经酶切和电泳鉴定正确后,在大肠杆菌BL21(DE3)中诱导表达,表达产物经亲和层析、离子交换层析及凝胶过滤等方法分离纯化。最后用SDS—PAGE和DNA降解实验进行鉴定。结果构建了pCool—GST—ICAD/CAD原核表达载体,重组载体转化后表达出毫克级水平的GST—ICAD/CAD蛋白复合体。经分离纯化后得到纯度很好的CAD—ICAD篮白复合体,在SDS—PAGE电泳上旱现清晰的两条蛋白带。经DNA降解实验证明纯化所得的CAD蛋白具有非特异性降解DNA的核酸酶作用。结论成功制备了具有生物学活性的CAD核酸酶,为进一步研究细胞凋亡的作用机制提供了有效的制剂。  相似文献   
5.
重组人生长激素降解产物的检测分析   总被引:1,自引:1,他引:0  
本文详细介绍了S-B电导率模型确定泥质砂岩储层含水饱和度的基本原理以及相应参数的确定方法。用该方法处理了大庆地区的树131井、萨南5丁4-检132井及杏9丁3检134井的一些层位,并将求得的含水饱和度与岩心分析的含水饱和度进行了对比,吻合得比较好。这说明了应用S-B模型确定储层的含水饱和度是可行的,结果比较好。  相似文献   
6.
Background: Fluctuations in the level of mite allergens in domestic house dust are the result of changes in the balance between synthesis, removal and decay. Purely physical forces as well as enzymatic degradation, mediated by house dust inhabiting microbes, may contribute to the decay of allergens in domestic dust. Knowledge about the speed of decay is essential for an understanding of the dynamics of allergen levels. Objective: The present study is a quantitative assessment of the speed of decay at nine combinations of temperature (15°C, 20°C and 25°C) and relative humidity (33%, 55% and 75%). Methods: Samples of mite infested material of an old rug were stored at these temperature/relative humidity-combinations for 6, 12 or 18 months, after the mites were killed by cither a freezing treatment or an acaricide (lindane). The microbes living in the rug presumably survive these treatments. Concentrations of Der p I and Der p II + Der f II. in extracts of the rug material, were measured by a radio immunoassay. Results: No significant changes in the levels of Der p I and Der p II +Der f II, could be detected even after 11/2 year at a high temperature and humidity. Conclusion: These findings incidate that mite allergens can be extremely stable under normal domestic circumstances.  相似文献   
7.
1. The mechanism of action of drugs might change according to the test used. Several noradrenergic drugs were tested in order to understand their implication in the mobility tests.

2. It was found that clonidine, an Alpha 2 agonist, acted differently according to the tast used. It provoked sedation in spontaneous activity test, and anti-immobility effects in the other tests.

3. Tall suspension test is able to show the double acting of clonidine.

4. Idazoxan might act either as an alpha 2 antagonist or as partial alpha 2 agonist. TST shown the unexpected partial alpha agonist effect of the molecule.

5. Forced swimming test is more specific for predicting antidepressant activity than tail suspension test which is close to a spontaneous activity model.  相似文献   

8.
Background. A single deep inspiration (DI) is known to be a potent bronchodilator but it is not known if repeated DI can accelerate sustained recovery from bronchoconstriction. Methods. We induced sustained bronchoconstriction using increasing concentrations of nebulized methacholine (Mch) during tidal breathing and assessed airway narrowing by measuring respiratory resistance (Rrs) using forced oscillation in six healthy subjects. On separate days we examined the effects of DI every 3 minutes and of prohibition of DI on recovery of Rrs for 30 minutes after the end of Mch nebulization. Results. Bronchoconstriction (Rrs ∼ 150% above baseline) was induced. DI during recovery had a transient bronchodilator effect but no cumulative effect. At 30 minutes after end of nebulization (and 2 minutes after the last DI) Rrs was 87% above baseline compared to 93% above baseline when DI was prohibited. Conclusion. Recovery from induced bronchoconstriction with methacholine was slow (∼ 2%/min) and not accelerated by frequent DI.  相似文献   
9.
A number of factors affecting the stability of propranolol HC1 during electrophoretic control were investigated. It was found that significant degradation of propranolol HC1 and hydrolysis of water occurred when a current of 15 mA was used with platinized electrodes. This degradation was thought to be due to decomposition of propranolol HC1 at the electrodes. Degradation could be significantly reduced by using uncoated platinum electrodes and currents in the range of 0 to 2.5 mA, while still allowing control of drug delivery rates. Electrode reaction processes were found at high ionic strengths and high drug concentrations but were not thought to be associated with drug decomposition.  相似文献   
10.
Hemoglobin-heme is variably converted to porphyrin during enterocolic transit. This intestinal converted fraction, as measured by HemoQuant, was elevated as a predictor of the occult bleeding site in 152 patients with discrete lesions. The intestinal converted fraction, expressed as the percentage of total fecal hemoglobin, was similar with upper gastrointestinal and proximal colon lesions. Within the colon, values trended downward with more distal location: means ± standard deviations were 18±14 proximal colon, 16 ±15 sigmoid, and 10±10 rectum. The amount of fecal blood also affected the intestinal converted fraction; correcting for hemoglobin concentration improved separation by site. Corrected intestinal converted fraction values were significantly lower with rectal (P< 0.0005) and sigmoid (P<0.02) lesions than with proximal colon lesions. Unfortunately, large within-site variation caused considerable overlap between sites. We conclude that the intestinal converted fraction is influenced by the site and amount of bleeding. However, its clinical utility is compromised by substantial individual differences in luminal hemoglobin metabolism.Presented in part at the Annual meeting of the American Gastroenterological Association in San Francisco in May of 1986 (Gastroenterology 90:1431, 1986).Supported by the Mayo Foundation.  相似文献   
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