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31.
Gene profiling reveals increased expression of uteroglobin and other anti-inflammatory genes in glucocorticoid-treated nasal polyps 总被引:3,自引:0,他引:3
Benson M Carlsson L Adner M Jernås M Rudemo M Sjögren A Svensson PA Uddman R Cardell LO 《The Journal of allergy and clinical immunology》2004,113(6):58-1143
BACKGROUND: Treatment with local glucocorticoids (GCs) decreases symptoms and the size of nasal polyps. This might depend on the downregulation of proinflammatory genes, as well as the upregulation of anti-inflammatory genes. OBJECTIVE: We sought to identify GC-regulated anti-inflammatory genes in nasal polyps. METHODS: Affymetrix DNA microarrays were used to analyze the expression of 22,283 genes in 4 nasal polyps before and after local treatment with fluticasone (400 microg/d). Expression of uteroglobin and mammaglobin B was analyzed with real-time PCR in 6 nasal polyps and in nasal biopsy specimens from 6 healthy control subjects. RESULTS: Two hundred three genes had changed in expression in treated polyps, and 139 had known functions: 54 genes were downregulated, and 85 were upregulated. Genes associated with inflammation constituted the largest single functional group. These genes affected key steps in inflammation (eg, immunoglobulin production; antigen processing and presentation; and the chemoattraction and activation of granulocytes, T cells, and B cells). Several proinflammatory genes were downregulated. In contrast, some anti-inflammatory genes were upregulated. The gene that increased most in terms of expression was uteroglobin. This was confirmed with real-time PCR. By contrast, expression of uteroglobin was lower in untreated polyps than in healthy nasal mucosa. Immunohistochemical investigation showed staining of uteroglobin in the epithelium and in seromucous glands in control subjects and in nasal polyps. CONCLUSION: Upregulation of anti-inflammatory genes, such as uteroglobin, might contribute to the effects of local treatment with GCs in nasal polyps. 相似文献
32.
Caroline E Wright Katie O'Donnell Lena Brydon Jane Wardle Andrew Steptoe 《International journal of psychophysiology》2007,63(3):275-282
Heightened cardiovascular stress responsivity is associated with cardiovascular disease, but the origins of heightened responsivity are unclear. The present study investigated whether disturbances in cardiovascular responsivity were evident in individuals with a family history of cardiovascular disease risk. Data were collected from 60 women and 31 men with an average age of 21.4 years. Family history of cardiovascular disease risk was defined by the presence of coronary heart disease, hypertension, diabetes or high cholesterol in participants' parents and grandparents; 75 participants had positive, and 16 had negative family histories. Systolic and diastolic blood pressure (BP), heart rate and heart rate variability were measured continuously for 5 min periods at baseline, during two mental stress tasks (Stroop and speech task) and at 10-15 min, 25-30 min and 40-45 min post-stress. Individuals with a positive family history exhibited significantly greater diastolic BP reactivity and poorer systolic and diastolic BP recovery from the stressors in comparison with family history negative individuals. In addition, female participants with a positive family history had heightened heart rate and heart rate variability reactivity to stressors. These effects were independent of baseline cardiovascular activity, body mass index, waist to hip ratio and smoking status. Family history of hypertension alone was not associated with stress responsivity. The findings indicate that a family history of cardiovascular disease risk influences stress responsivity which may in turn contribute to risk of future cardiovascular disorders. 相似文献
33.
34.
Berhane K Karim R Cohen MH Masri-Lavine L Young M Anastos K Augenbraun M Watts DH Levine AM 《Journal of acquired immune deficiency syndromes (1999)》2004,37(2):1245-1252
BACKGROUND: Anemia is common in HIV-infected individuals and may be associated with decreased survival. OBJECTIVE: To ascertain the impact of highly active antiretroviral therapy (HAART) on anemia and the relationship between anemia and overall survival in HIV-infected women. METHODS: A prospective multicenter study of HIV-1 infection in women. Visits occurred every 6 months, including a standardized history, physical examination, and comprehensive laboratory evaluation. The setting was a university-affiliated clinic at 6 sites in the United States. Participants were 2056 HIV-infected women from the Women's Interagency HIV Study (WIHS). The outcome measure was anemia, defined as hemoglobin (Hb) <12 g/dL. Survival analysis was based on overall mortality during the follow-up period. RESULTS: Among HIV-infected women who were not anemic at baseline, 47% became anemic by 3.5 years of follow-up. On multivariate analysis, the use of HAART was associated with resolution of anemia even when used for only 6 months (odds ratio [OR] = 1.45; P < 0.05). In the multivariate model, a CD4 cell count <200 cells/microL (OR = 0.56; P < 0.001); HIV-1 RNA level > or =50,000 copies/mL (OR = 0.65; P < 0.001), and mean corpuscular volume (MCV) value <80 fL (OR = 0.40; P < 0.001) were also associated with an inability to correct anemia. Similarly, use of HAART for 12 months or more was associated with a protective effect against development of anemia (OR = 0.71; P < 0.001). Among HIV-infected women, anemia was independently associated with decreased survival (hazard ratio [HR] = 2.58; P < 0.001). Other factors associated with decreased survival included a CD4 cell count <200 cells/microL (HR = 5.83; P < 0.001), HIV-1 RNA level > or = 50,000 copies/mL (HR = 2.12; P < 0.001), and clinical diagnosis of AIDS (HR = 2.83; P < 0.001). CONCLUSIONS: Anemia is an independent risk factor for decreased survival among HIV-infected women. HAART therapy for as little as 6 months is associated with resolution of anemia. 相似文献
35.
Kinetic studies of neutrophil phagocytosis: V. Studies on the co-operation between the Fc and C3b receptors 总被引:4,自引:0,他引:4
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The co-operation between the Fc and C3b receptors of PMNs (neutrophil granulocytes) during phagocytosis has been studied by the effect of interference with either of the receptors. The significance of the Fc receptor for the mediation of internalization proposed by previous investigators was confirmed by the inhibition of both Fc- and C3b-mediated phagocytosis by Fc fragments of IgG and by Fab fragments of antiserum against the Fc part of IgG. C3b-receptor-mediated phagocytosis was inhibited by trypsin, granulocyte elastase, myeloperoxidase and H2O2. High concentrations of elastase and the combined action of H2O2 and myeloperoxidase generated a C3b-receptor dysfunction, which implied that the destruction of C3b-receptor function also disturbed Fc-receptor function. The demonstrated C3b receptor dysfunction indicated that the Fc and C3b receptors were closely situated in the cellular membrane of the PMN. A hypothesis for co-operation between the two receptor types would be that the C3b receptor initially facilitates the adherence of an IgG-C3b-coated particle. Secondly, the C3b receptor would facilitate the IgG-Fc-receptor contact either by some kind of structural derangement to permit the entrance of the IgG-C3b complex or by removal of C3b from the Fc part of IgG. 相似文献
36.
Coexistence of NMDA and AMPA receptor subunits with nNOS in the nucleus tractus solitarii of rat 总被引:3,自引:0,他引:3
We previously showed that most neuronal nitric oxide synthase (nNOS)-containing neurons in the nucleus tractus solitarii (NTS) contain NMDAR1, the fundamental subunit for functional N-methyl-D-aspartate (NMDA) receptors. Likewise, we found that almost all nNOS-containing neurons in the NTS contain GluR1, the calcium permeable AMPA receptor subunit. These data suggest that AMPA and NMDA receptors may colocalize in NTS neurons that contain nNOS. However, other investigators have suggested that non-NMDA receptors are located primarily on second-order neurons and NMDA receptors are located predominantly on higher-order neurons in NTS. We now seek to test the hypothesis that NMDA receptors, AMPA receptors and nNOS are colocalized in NTS cells. We performed triple fluorescent immunohistochemical staining of nNOS, NMDAR1 and GluR1, and performed confocal laser scanning microscopic analysis of the NTS. The distributions of nNOS immunoreactivity (IR), NMDAR1-IR and GluR1-IR in the NTS were similar to those we reported earlier. Superimposed images revealed that almost all NMDAR1-IR cells contained GluR1-IR and almost all GluR1-IR cells contained NMDAR1-IR. Some double-labeled cells were additionally labeled for nNOS-IR. All nNOS-IR neurons contained both GluR1-IR and NMDAR1-IR. These studies support our hypothesis that NMDA and AMPA receptors are colocalized in NTS neurons and are consistent with a role of both types of ionotropic receptors in transmission of afferent signals in NTS. In addition, these data provide support for an anatomical link between ionotropic glutamate receptors and nitric oxide in the NTS. 相似文献
37.
Exposure in swine confinement buildings induces an intense airway inflammation. Twenty-two volunteers, of whom eleven wore
a half-mask, were exposed for 3 hr in a swine barn. Blood samples were drawn before and after exposure. The ratio C3b/totalC3
in plasma decreased from 6.8 to 5.0% (p = 0.02) without mask and from 6.6 to 5.9% (p = 0.01) with mask (p = 0.67 between groups). The ratio Bb/totalB decreased from 14.5 to 13.5% (p < 0.01) without and 14.6–13.3% (p = 0.09) with mask (p = 0.25 between groups). Epithelial cells (A549) incubated up to 24 hr with 0.1 mg/mL dust suspensions were analysed for C3,
IL-6 and IL-8 secretion. Cumulative C3 synthesis of dust stimulated cell cultures was 43,000 pg/mL compared to 25,000 pg/mL
in unstimulated cells. Cumulative dust-induced IL-6 and IL-8 secretion was 200 and 3000 pg/mL, respectively and below detection
in unstimulated cells.The activation of complement in vivo and induced C3 synthesis by epithelial cells suggests a role of complement in the airway reaction to organic dust exposure. 相似文献
38.
CD1d-restricted natural killer T cells are potent targets for human immunodeficiency virus infection 总被引:1,自引:0,他引:1
Invariant human natural killer T cells (NKT) express a restricted T-cell receptor (TCR) Valpha24Vbeta11 repertoire. These cells share both phenotypic and functional similarities between NK and T cells. Given the emerging role of NKT cells as critical cells in bridging the gap between innate and adaptive immunity, we examined their susceptibility to productive human immunodeficiency virus (HIV) infection by T-tropic, M-tropic, and primary isolates of HIV. We generated three human NKT cell clones (CA5, CA29, and CA31). Phenotypic characterization of these Valpha24+ Vbeta11+ clones indicated that they were predominately positive for CD4, CD161, HLA-DR, CD38, CD45RO, and CD95 expression. The NKT cell clones expressed significantly more surface CCR5 molecules/cell and lower CXCR4 molecules/cell than phytohaemagglutinin-stimulated peripheral blood mononuclear cells (PBMC). Consistent with the surface expression of CCR5 and CXCR4, the NKT clones were also selectively susceptible to HIV M-tropic, T-tropic, and primary isolate infection, as evaluated by both HIV p24 enzyme-linked immunosorbent assay and intracellular staining of HIV proteins. The amount of p24 production was dependent on the NKT clone studied and the HIV strain used. Clones CA29 and CA31 were also susceptible to HIV IIIB infection. The virions produced by these clones were able to productively infect PHA-stimulated PBMCs with the same kinetics as for primary infection of CD4+ blast. Collectively, this data demonstrates that NKT cells can be a target for productive HIV infection but with a lag in the time to peak p24 production. 相似文献
39.
Göran K. Hansson Göran Bondjers Anders Bylock Lena Hjalmarsson 《Experimental and molecular pathology》1980,33(3):302-315
Immunoelectron microscopy with peroxidase-conjugated Fab fragments of anti-IgG was used for studying the localization of IgG in the aortic endothelium and subendothelial intima of atherosclerotic and nonatherosclerotic rabbits. Small amounts of IgG were found in the cell coat, in caveolae and vesicles, and also in intercellular clefts of endothelial cells from normocholesterolemic rabbits. Injured endothelial cells exhibited prominent accumulations of IgG in the cytoplasmic matrix, possibly due to leakage through plasma membrane defects. In atherosclerotic lesions from hypercholesterolemic rabbits, there was a striking increase in the amount of IgG-reactive material in the cell coat and vesicles of intact endothelial cells. Also in these animals, injured endothelial cells were characterized by a cytoplasmic IgG accumulation. There were prominent IgG depositions in the subendothelial zone of the lesions. IgG was adhering to collagen fibers, and also coating the surfaces of subendothelial foam cells. The pathophysiological significance of an interaction between such intimal IgG and phagocytes is discussed. 相似文献
40.
An adult patient presented with vesicular rash and abdominal pain of 5 days duration. His initial laboratory results showed elevated liver enzymes. A contrast enhanced CT scan demonstrated multiple small hypodense nodules in liver and spleen. His serum was reactive for Varicella Zoster IgM. Patient was treated with intravenous Acyclovir for 5 days and followed up with oral tablets for 2 weeks. At 3 weeks, CT scan showed resolution of hypodense nodules and his serum liver enzymes returned to normal at 6 weeks. Patient is on follow up and asymptomatic for 2 years. The CT appearances of nodules and their resolution following specific antiviral therapy are useful in diagnosis and in follow up of disseminated Varicella Zoster. 相似文献