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961.
Tang JR Le Cras TD Morris KG Abman SH 《American journal of physiology. Lung cellular and molecular physiology》2000,278(2):L356-L364
We hypothesized that disrupted alveolarization and lung vascular growth caused by brief perinatal hypoxia would predispose infant rats to higher risk for developing pulmonary hypertension when reexposed to hypoxia. Pregnant rats were exposed to 11% inspired oxygen fraction (barometric pressure, 410 mmHg; inspired oxygen pressure, 76 mmHg) for 3 days before birth and were maintained in hypoxia for 3 days after birth. Control rats were born and raised in room air. At 2 wk of age, rats from both groups were exposed to hypoxia for 1 wk or kept in room air. We found that brief perinatal hypoxia resulted in a greater increase in right ventricular systolic pressure and higher ratio of right ventricle to left ventricle plus septum weights after reexposure to hypoxia after 2 wk of age. Moreover, perinatal hypoxic rats had decreased radial alveolar counts and reduced pulmonary artery density. We conclude that brief perinatal hypoxia increases the severity of pulmonary hypertension when rats are reexposed to hypoxia. We speculate that disrupted alveolarization and lung vascular growth following brief perinatal hypoxia may increase the risk for severe pulmonary hypertension with exposure to adverse stimuli later in life. 相似文献
962.
The regulation of pro- and anti-mediator release from cells within the alveolar space would represent a desirable mechanism serving to protect this delicate gas-exchanging region of the lung. This study investigates the effect of alveolar surfactant lipids on the regulation of tumour necrosis factor alpha (TNF-alpha), a potent inflammatory cytokine, and prostaglandin E(2)(PGE(2)), a lipid mediator with anti-inflammatory properties. The results of this investigation reveal a marked effect on the release of these two important mediators from a monocytic cell line, MonoMac 6 (MM6), by phosphatidylcholine (PC), phosphatidylethanolamine (PE), cholesterol (Chol) and sphingomyelin (SM). PC, PE and Chol demonstrated marked downregulation of TNF-alpha production at lipid concentrations of 125 and 250 microg/ml. Interestingly, SM significantly up regulated the release of TNF-alpha at these concentrations. However, the release of PGE(2)in MM6 cells incubated with the same lipids was significantly increased with PC and Chol, and significantly decreased in cells pre-treated with SM. This indicates a role for these lipids in alveolar immunoregulation. 相似文献
963.
IL-4 and IL-13 upregulate arginase I expression by cAMP and JAK/STAT6 pathways in vascular smooth muscle cells 总被引:7,自引:0,他引:7
Wei LH Jacobs AT Morris SM Ignarro LJ 《American journal of physiology. Cell physiology》2000,279(1):C248-C256
The objectives ofthis study were to determine whether rat aortic smooth muscle cells(RASMC) express arginase and to elucidate the possible mechanismsinvolved in the regulation of arginase expression. The results showthat RASMC contain basal arginase I (AI) activity, which issignificantly enhanced by stimulating the cells with either interleukin(IL)-4 or IL-13, but arginase II (AII) expression was not detectedunder any condition studied here. We further investigated the signaltransduction pathways responsible for AI induction. AI mRNA and proteinlevels were enhanced by addition of forskolin (1 µM) and inhibited byH-89 (30 µM), suggesting positive regulation of AI by aprotein kinase A pathway. Genistein (10 µg/ml) and sodiumorthovanadate (Na3VO4; 10 µM) were used toinvestigate the role of tyrosine phosphorylation in the control of AIexpression. Genistein inhibited, whereas Na3VO4enhanced the induction of AI by IL-4 or IL-13. Along with immunoprecipitation and immunoblot analyses, these data implicate theJAK/STAT6 pathway in AI regulation. Dexamethasone (Dex) and interferon(IFN)- were investigated for their effects on AI induction. Dex (1 µM) and IFN- (100 U/ml) alone had no effect on basal AI expressionin RASMC, but both reduced AI induction by IL-4 and IL-13. Incombination, Dex and IFN- abolished AI induction by IL-4 and IL-13.Finally, both IL-4 and IL-13 significantly increased RASMC DNAsynthesis as monitored by [3H]thymidine incorporation,demonstrating that upregulation of AI is correlated with an increase incell proliferation. Blockade of AI induction by IFN-, H-89, orgenistein also blocked the increase in cell proliferation. Theseobservations are consistent with the possibility that upregulation ofAI might play an important role in the pathophysiology of vasculardisorders characterized by excessive smooth muscle growth. 相似文献
964.
Properties of CFTR activated by the xanthine derivative X-33 in human airway Calu-3 cells 总被引:1,自引:0,他引:1
Bulteau L Dérand R Mettey Y Métayé T Morris MR McNeilly CM Folli C Galietta LJ Zegarra-Moran O Pereira MM Jougla C Dormer RL Vierfond JM Joffre M Becq F 《American journal of physiology. Cell physiology》2000,279(6):C1925-C1937
The pharmacological activation of thecystic fibrosis gene protein cystic fibrosis transmembrane conductanceregulator (CFTR) was studied in human airway epithelial Calu-3 cells,which express a high level of CFTR protein as assessed by Western blotand in vitro phosphorylation. Immunolocalization shows that CFTR islocated in the apical membrane. We performed iodide efflux, whole cell patch-clamp, and short-circuit recordings to demonstrate that the novelsynthesized xanthine derivative 3,7-dimethyl-1-isobutylxanthine (X-33)is an activator of the CFTR channel in Calu-3 cells. Whole cell currentactivated by X-33 or IBMX is linear, inhibited by glibenclamide anddiphenylamine-2-carboxylate but not by DIDS or TS-TM calix[4]arene.Intracellular cAMP was not affected by X-33. An outwardly rectifyingCl current was recorded in the absence of cAMP and X-33stimulation, inhibited by DIDS and TS-TM calix[4]arene. With the useof short-circuit recordings, X-33 and IBMX were able to stimulate alarge concentration-dependent CFTR transport that was blocked byglibenclamide but not by DIDS. Our results show that manipulating thechemical structure of xanthine derivatives offers an opportunity toidentify further specific activators of CFTR in airway cells. 相似文献
965.
966.
Injection of the rat with guinea pig myelin basic protein (MBP) induces an inflammatory demyelination that leads to development of a condition mimicking human multiple sclerosis (MS), including severe depressions in mobility, coordination, and strength in the affected animal. This model was used to observe and compare the antiinflammatory effects of the intestinal and late migratory phases of infection with Trichinella pseudospiralis on development of MBP-induced, MS-like debilitation in rats. Animal performance was measured in an activity monitor and in a series of physical tests designed to assess animal coordination and strength. Uninfected animals injected with MBP showed declines in mobility, coordination, and strength typical for this model. These changes were similar in rats infected so that the intestinal phase of infection coincided with the peak of MBP-induced debilitation. Rats infected so that the late migratory phase of infection occurred during the period of peak MBP-induced debilitation showed significantly higher performance scores in mobility, coordination and strength compared to the latter 2 groups. These finding demonstrate the potency of the anti-inflammatory effects of elevations in host corticosteroids seen during the migratory phase of infection with T. pseudospiralis. 相似文献
967.
968.
969.
Identification of an N-Terminal Region of Sigma 54 Required for Enhancer Responsiveness 总被引:4,自引:3,他引:1 下载免费PDF全文
Sigma 54 associates with bacterial core RNA polymerase and converts it into an enhancer-responsive enzyme. Deletion of the N-terminal 40 amino acids is known to result in loss of the ability to respond to enhancer binding proteins. In this work PCR mutagenesis and genetic screens were used to identify a small patch, from amino acids 33 to 37, that is required for proper response to activator in vivo. Site-directed single point mutants within this segment were constructed and studied. Two of these were defective in responding to the enhancer binding protein in vitro. The mutants could still direct the polymerase to bind to DNA and initiate transient melting. However, they failed in directing activator-dependent formation of a heparin-stable open complex. Thus, amino acid region 33 to 37 includes critical activation response determinants. This region overlaps the larger leucine patch negative-control region, suggesting that anti-inhibition and positive activation are closely coupled events. 相似文献
970.
Current methods for stallion semen cryopreservation: a survey 总被引:1,自引:0,他引:1
Various factors affect the success of AI with frozen-thawed semen in horses. Stallion variability is thought to be one of the major factors, but semen processing and evaluation techniques, thawing protocols, packaging systems and timing of insemination are far from standardized among laboratories. Our objective was to survey current methods for stallion semen cryopreservation used commercially around the world. From the answers to the questions in the survey, we attempted to provide an overview of procedures that are standard as well as those that are used by only few laboratories and to review critically the efficacy of these procedures. Twenty-five questionnaires were sent to individuals or laboratories in 14 countries that were i.v. involved in freezing stallion semen for commercial purposes. Questionnaires were returned from 10/14 countries with 21/25 (84%) of the addresses responding. From the responses, it became evident that most of prefreezing, freezing and thawing and post-thawing processing procedures were far from standardized. The great variety of procedures makes it difficult to accept any of them as reliable. In order to increase the credibility of AI technology in the horse, laboratories need to standardize processing methods as well as the record-keeping systems. In addition, it is evident that no group of research mares is large enough to provide meaningful fertility data. It is therefore imperative to have multicentered collaborative studies to record and disseminate information about methods and the corresponding fertility rate. to gain valuable information and be able to compare different protocols. 相似文献