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991.
BACKGROUND: Chronic inflammation and infection in patients with cystic fibrosis (CF) and other lung diseases begin early, making noninvasive diagnostic techniques vital. As induced sputum (IS) testing is useful in older patients, we investigated its adaptation to young nonexpectorating children. METHODS: Following the inhalation of a 4.5% saline solution, sputum was collected by nasopharyngeal or oropharyngeal suction for culture and testing for inflammatory markers, with paired preceding oropharyngeal cough swabs (OCSs) in a subgroup. Specimens from 48 IS procedures (46 successful) in 20 CF children (median age, 3 years) were compared with 8 specimens from 8 non-CF pulmonary patients (median age, 4.5 years). RESULTS: The procedure was safe, with arterial oxygen saturation remaining at > or = 96%. Cultures from 14 of 46 CF patients (30%) grew Pseudomonas aeruginosa, whereas cultures from 19 of 46 CF patients (41%) had no growth. Cultures from seven of eight non-CF subjects grew bacteria, but none were P aeruginosa. Comparing 29 paired IS and OCS samples, 11 and 5 samples, respectively, cultured P aeruginosa (not significant), whereas 12 and 21 samples, respectively, had no growth (p = 0.02). A correlation was found between the independent inflammatory markers NE and both interleukin (IL)-8 (r = 0.85; p < 0.001) and the percentage of neutrophils (r = 0.35; p < 0.05), confirming the validity of IS samples in evaluating early airway disease. IL-8 levels also increased with age (r = 0.41; p < 0.05). Inflammation was similar in CF and non-CF subjects. CONCLUSIONS: IS testing in the young is feasible, safe, and clinically useful, and could serve as an outcome measure for new therapies. 相似文献
992.
CD70 and IFN‐1 selectively induce eomesodermin or T‐bet and synergize to promote CD8+ T‐cell responses 下载免费PDF全文
Han Dong Nathan A. Franklin Shane B. Ritchea Hideo Yagita Martin J. Glennie Timothy N. J. Bullock 《European journal of immunology》2015,45(12):3289-3301
CD70‐mediated stimulation of CD27 is an important cofactor of CD4+ T‐cell licensed dendritic cells (DCs). However, it is unclear how CD70‐mediated stimulation of T cells is integrated with signals that emanate from signal 3 pathways, such as type‐1 interferon (IFN‐1) and IL‐12. We find that while stimulation of CD27 in isolation drives weak EomesoderminhiT‐betlo CD8+ T‐cell responses to OVA immunization, profound synergistic expansion is achieved by cotargeting TLR. This cooperativity can substantially boost antiviral CD8+ T‐cell responses during acute infection. Concomitant stimulation of TLR significantly increases per cell IFN‐γ production and the proportion of the population with characteristics of short‐lived effector cells, yet also promotes the ability to form long‐lived memory. Notably, while IFN‐1 contributes to the expression of CD70 on DCs, the synergy between CD27 and TLR stimulation is dependent upon IFN‐1's effect directly on CD8+ T cells, and is associated with the increased expression of T‐bet in T cells. Surprisingly, we find that IL‐12 fails to synergize with CD27 stimulation to promote CD8+ T‐cell expansion, despite its capacity to drive effector CD8+ T‐cell differentiation. Together, these data identify complex interactions between signal 3 and costimulatory pathways, and identify opportunities to influence the differentiation of CD8+ T‐cell responses. 相似文献
993.
Previously, we reported that activation of the human prolactin receptor (PRLR) produced a protein phosphorylation pattern
strikingly similar to that provoked by Concanavalin A (Con A), an activator of the T-cell antigen receptor (TCR). These results
suggested that certain signaling components of the TCR may be shared by the activated PRLR. Additional studies here assessed
the levels of TCR expression following PRLR stimulation and the effect of TCR activation on PRL-stimulated proliferation in
lactogen-dependent pre-T Nb2-11 lymphoma cells. The results indicated that the TCR was expressed on the surface of approx
4% of exponentially proliferating and prolactin- (PRL) treated cells. In contrast, approx 45% of quiescent cells, cultured
in the absence of PRL for 24 h, expressed the TCR at the cell surface, suggesting that lactogen withdrawal may up-regulate
TCR cell-surface expression. Moreover, TCR activation with anti-CD3 antibodies attenuated PRL-stimulated Nb2-11 cell proliferation
in a concentration-dependent manner. In other experiments, immunoprecipitation and immunoblotting of Nb2-11 lysates revealed
that activation of the PRLR resulted in rapid tyrosyl phosphorylation of ZAP-70, a critical TCR-associated tyrosine kinase.
In addition, ZAP-70 was found to associate transiently with the putative guanine nucleotide exchange factor and substrate,
Vav, in PRL-treated cells. ZAP-70 was also found to associate constitutively with the PRLR; PRL stimulation provoked the transient
recruitment of Vav to the complex. These observations suggest that PRL signaling reflects the transient formation of a PRLR-ZAP-70-Vav
complex and its immunomodulatory actions involve diverse interactions that affect TCR expression and signaling mechanisms. 相似文献
994.
995.
目的探讨卡介苗热休克蛋白70(BCG HSP70)基因转染对小鼠淋巴细胞白血病细胞(L1210)致瘤性及免疫原性的影响。方法利用脂质体2000将BCG HSP70基因转入小鼠淋巴细胞白血病细胞系L1210表面,获得高表达HSP70分子的L1210-HSP70细胞,作为肿瘤疫苗分别对裸鼠及同系小鼠致瘤性、瘤苗对荷瘤小鼠的免疫治疗作用以及瘤苗对L1210细胞攻击的免疫保护作用进行研究。结果 BCG HSP70成功表达在转染后的L1210细胞表面,并具有与野生型细胞同样的致瘤性。同系小鼠DBA/2皮下接种L1210-HSP70细胞后肿瘤生长缓慢或不成瘤;相对于L1210组和L1210-neo组,生存期明显延长,小鼠脾淋巴细胞中针对L1210细胞的特异性T细胞数量明显增加,差异有统计学意义(P0.05);瘤体病理切片示彻底凝固性坏死,周边可见淋巴样细胞,免疫组化检测示大量CD8+T淋巴细胞浸润。L1210-HSP70细胞瘤苗具有对荷瘤小鼠的免疫治疗作用,以及抗肿瘤攻击的免疫保护作用,均表现为肿瘤出瘤时间明显延长,生长受到显著抑制,瘤体平均直径明显减小;荷瘤小鼠生存时间明显长于L1210组、L1210-neo组和PBS组,差异有统计学意义(P0.05)。结论BCG HSP70基因转染能有效增强肿瘤细胞的免疫原性,激活特异性T细胞,降低肿瘤细胞的致瘤性;并具有提高宿主抗瘤免疫作用。 相似文献
996.
BACKGROUND: Periodic breathing (PB) in heart failure (HF) is attributed to many factors, including low cardiac output delaying the time it takes pulmonary venous blood to reach the central and peripheral chemoreceptors, low lung volume, lung congestion, augmented chemoreceptor sensitivity, and the narrow difference between eupneic carbon dioxide tension and apneic/hypoventilatory threshold. METHODS AND RESULTS: We measured expired gases, ventilation, amplitude, and duration of PB in 23 patients with PB during progressive exercise tests done with 0 mL, 250 mL, or 500 mL of added dead space. Periodicity of PB remained constant despite heart rate, oxygen consumption, and minute ventilation increasing. Within each PB cycle, starting from the beginning of exercise, the largest (peak) tidal volume approached maximum observed tidal volume, while the smallest (nadir) tidal volume increased as exercise power output increased. PB ceased when nadir tidal volume reached peak tidal volume. End-tidal carbon dioxide increased with added dead space, and PB ceased progressively earlier during the exercise done with increased dead space. CONCLUSION: Circulatory delay does not contribute to the PB observed in exercising HF patients. The pattern of gradually increasing nadir tidal volume during exercise and the effect of dead space on both PB ceasing and end-tidal carbon dioxide suggest that low tidal volume and carbon dioxide apnea threshold are important contributors to PB that occurs during exercise in HF. 相似文献
997.
BACKGROUND: The use of antiplatelet therapy in combination with oral anticoagulants remains controversial. The objective of this study was to estimate and compare the incidence of adverse and coronary event rates between patients receiving warfarin monotherapy or warfarin and antiplatelet combination therapy. METHODS: This was a retrospective, longitudinal, pharmacoepidemiologic analysis. Adult patients receiving warfarin managed by an anticoagulation service who had documented the use of antiplatelet agents (eg, aspirin, clopidogrel, and/or dipyridamole) [ie, the combination-therapy cohort] or their nonuse (ie, the monotherapy cohort) were identified as of September 30, 2005. Utilizing integrated, electronic medical records, anticoagulation-related adverse events (eg, death, hemorrhage, or thrombosis) and coronary events were identified during a 6-month follow-up period (October 2005 through March 2006). The proportions of events were compared between cohorts. Independent associations between the cohorts and the outcomes were assessed with adjustment for potential confounding factors. RESULTS: Data from 2,560 patients in the monotherapy cohort and 1,623 patients in the combination-therapy cohort were analyzed. Patients in the combination-therapy cohort were more likely to have had anticoagulation-related hemorrhages (4.2% vs 2.0%, respectively; unadjusted p < 0.001) and coronary events (0.9% vs 0.3%, respectively; p = 0.009), but not death (0.1% vs 0.2%, respectively; unadjusted p = 0.186) or thrombotic events (0.3% vs 0.4%, respectively; unadjusted p = 0.812). With adjustment, combined warfarin and antiplatelet use was independently associated with hemorrhagic events (odds ratio [OR], 2.75; 95% confidence interval [CI], 1.44 to 5.28), but not with coronary events (OR, 0.99; 95% CI, 0.37 to 2.62). CONCLUSIONS: At the population level, the hemorrhagic risk associated with warfarin therapy combined with antiplatelet therapy appears to outweigh the benefits. These findings suggest that clinicians should carefully consider the risks and benefits when recommending combined antiplatelet therapy for patients receiving warfarin who do not meet the evidence-based criteria for such therapy. 相似文献
998.
BACKGROUND: Low tidal volume (Vt) ventilation for ARDS is a well-accepted concept. However, controversy persists regarding the optimal ventilator settings for patients without ARDS receiving mechanical ventilation. This study tested the hypothesis that ventilator settings influence the development of new ARDS. METHODS: Retrospective analysis of patients from the Multi Parameter Intelligent Monitoring of Intensive Care-II project database who received mechanical ventilation for > or = 48 h between 2001 and 2005. RESULTS: A total of 2,583 patients required > 48 h of ventilation. Of 789 patients who did not have ARDS at hospital admission, ARDS developed in 152 patients (19%). Univariate analysis revealed high peak inspiratory pressure (odds ratio [OR], 1.53 per SD; 95% confidence interval [CI], 1.28 to 1.84), increasing positive end-expiratory pressure (OR, 1.35 per SD; 95% CI, 1.15 to 1.58), and Vt (OR, 1.36 per SD; 95% CI, 1.12 to 1.64) to be significant risk factors. Major nonventilator risk factors for ARDS included sepsis, low pH, elevated lactate, low albumin, transfusion of packed RBCs, transfusion of plasma, high net fluid balance, and low respiratory compliance. Multivariable logistic regression showed that peak pressure (OR, 1.31 per SD; 95% CI, 1.08 to 1.59), high net fluid balance (OR, 1.3 per SD; 95% CI, 1.09 to 1.56), transfusion of plasma (OR, 1.26 per SD; 95% CI, 1.07 to 1.49), sepsis (OR, 1.57; 95% CI, 1.00 to 2.45), and Vt (OR, 1.29 per SD; 95% CI, 1.02 to 1.52) were significantly associated with the development of ARDS. CONCLUSIONS: The associations between the development of ARDS and clinical interventions, including high airway pressures, high Vt, positive fluid balance, and transfusion of blood products, suggests that ARDS may be a preventable complication in some cases. 相似文献
999.
1000.
Lars Mueller Juliane Goettsche Awad Abdulgawad Yogesh K Vashist Jannine Meyer Christian Wilms Christian Hillert Xavier Rogiers Dieter C Broering 《Liver international》2005,25(5):994-1001
BACKGROUND/AIMS: Clinical observations suggest cancer progression after preoperative segmental portal vein occlusion, a procedure to prevent liver failure after major hepatic resections. The aim of this study was to determine whether portal occlusion induces host reactions which promote cancer invasion and angiogenesis. METHODS: The rat model of portal branch ligation (PBL) was compared with partial hepatectomy (PH) and sham operation (SO) and evaluated for the expression of heat shock protein-70 (hsp70), heme oxygenase-1 (hmox1), early growth response gene-1 (Egr-1) and urokinase-type plasminogen activator (uPA), its inhibitor (PAI-1) and receptor (uPAR). RESULTS: Portal deprivation after PBL was associated with a regression of liver tissue to 25% of its original mass within 8 days with only modest fibrotic changes. During the progression of atrophy, there were significant inductions of hsp70-, hmox1- and Egr-1-mRNA in comparison with regenerating liver tissue. PAI-1-specific mRNA was transiently elevated at 3 - 48 h after PBL in the atrophying lobes, whereas uPA and uPAR were unaffected in comparison with PH or SO. CONCLUSION: Hepatic atrophy caused by PBL is associated with increased expression of genes known to promote tumor growth. These host events represent a possible explanation for the tumor progression after portal occlusion and require further evaluation. 相似文献