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71.
A short open reading frame (ORF), ORF6, potentially encoding a polypeptide (pX) of 32–69 amino acids, was revealed upon computer translation of the 3 terminal regions of tomato bushy stunt, cymbidium ringspot, cucumber necrosis, and artichoke mottled crinkle tombusviruses. ORF6 has an initiating AUG codon in a favorable context and is evaluated as expressible, judging the distribution of guanosine residues within the codons. Inspection of the alignment of the four putative products encoded by ORF6 shows statistically significant sequence conservation over 11 SD above the random expectation. Secondary structure predictions based on the Garnier method demonstrate strict conservation of a loop between two -strands, thus suggesting functional conservation of pXs. It is suggested that pX is not involved in tombusvirus genome replication and encapsidation incis. 相似文献
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Erik Wennerberg Dhifaf Sarhan Mattias Carlsten Vitaliy O. Kaminskyy Padraig D'Arcy Boris Zhivotovsky Richard Childs Andreas Lundqvist 《International journal of cancer. Journal international du cancer》2013,133(7):1643-1652
Doxorubicin (DOX) is an anthracycline antibiotic that is widely used to treat different types of malignancy. In this study, it was studied whether DOX could be used to render tumor cells susceptible to apoptosis by NK and T cells. Pretreatment with subapoptotic doses of DOX sensitized tumor cell lines of various histotypes to both NK and T cells resulting in a 3.7 to 32.7% increase in lysis (2.5 mean fold increase, p < 0.0001) and a 2.9 to 14.2% increase in lysis (3.0 mean‐fold increase, p < 0.05), respectively. The sensitizing effect of the drug was primarily dependent on the tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)/TRAIL‐receptor signaling, but not on Fas‐ligand, perforin, NKG2D or DNAM‐1. The central role of the TRAIL signaling pathway was further supported by an increased expression of TRAIL‐R2 on DOX‐treated tumor cells and by downregulation of cellular FLICE inhibitory protein, the inhibitors of death receptor‐mediated apoptosis. Compared to untreated cells, pretreatment of tumor cells with DOX showed increased processing and activation of caspase‐8 on coculture with NK or T cells. The significance of this treatment strategy was confirmed using a xenogeneic tumor‐bearing mouse model. Tumor progression was delayed in mice that received either NK cells (p < 0.05) or T cells (p < 0.0001) following DOX treatment compared to mice receiving either cell type alone. Moreover, combined infusion of both NK and T cells following DOX treatment not only delayed tumor progression but also significantly improved the long‐term survival (p < 0.01). Based on these findings, it was proposed that DOX can be used to improve the efficacy of adoptive cell therapy in patients with cancer. 相似文献
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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising drug for the treatment of tumors; however, a number of cancer cells are resistant to this cytokine. Among the mechanisms of resistance of small cell lung carcinomas (SCLCs) to TRAIL is the lack of caspase-8 expression. Although methylation of the caspase-8 promoter has been suggested as the main mechanism of caspase-8 silencing, we showed that reduction of the enzymes involved in DNA methylation, DNA methyltransferases (DNMT) 1, 3a and 3b, was not sufficient to significantly restore caspase-8 expression in SCLC cells, signifying that other mechanisms are involved in caspase-8 silencing. We found that combination of the DNMT inhibitor decitabine with an inhibitor of histone deacetylase (HDAC) significantly increased caspase-8 expression in SCLC cells at the RNA and protein levels. Among all studied HDAC inhibitors, valproic acid (VPA) and CI-994 showed prolonged effects on histone acetylation, while combination with decitabine produced the most prominent effects on caspase-8 re-expression. Moreover, a significant reduction of survivin and cIAP-1 proteins level was observed after treatment with VPA. The combination of two drugs sensitized SCLC cells to TRAIL-induced apoptosis, involving mitochondrial apoptotic pathway and was accompanied by Bid cleavage, activation of Bax, and release of cytochrome c. Both initiator caspase-8 and -9 were required for the sensitization of SCLC cells to TRAIL. Thus, efficient restoration of caspase-8 expression in SCLC cells is achieved when a combination of DNMT and HDAC inhibitors is used, suggesting a combination of decitabine and VPA or CI-994 as a potential treatment for sensitization of SCLC cells lacking caspase-8 to TRAIL. 相似文献
77.
Patrick B. O’Neal Vitaliy Poylin Peter Mowschenson Sareh Parangi Gary Horowitz Pravin Pant Per-Olof Hasselgren 《World journal of surgery》2009,33(8):1665-1673
Background Inadequate fall in the intraoperative parathyroid hormone (PTH) level after removing enlarged parathyroid gland(s) typically
signifies additional hyperfunctioning gland(s), prompting further neck dissection, but it may also be a false negative result.
We analyzed intraoperative management of patients with an inadequate fall on PTH after excision of enlarged parathyroid gland(s).
Methods Analysis involved a prospective database of 189 patients undergoing 193 procedures for primary hyperparathyroidism. The PTH
level was determined before neck incision and 10–15 min after excision of enlarged parathyroid gland(s). A PTH decrease >
50% and into normal range was used as the criterion of successful parathyroidectomy.
Results In 48 of 193 operations, initial postexcision PTH level did not fall appropriately. That inadequate fall in PTH level was
a false negative result in 16 patients (33%) and cure was achieved without additional neck exploration in all but one patient,
who had additional (negative) neck exploration after excision of a parathyroid adenoma. In all patients with false negative
postexcision PTH assay, operative findings concurred with preoperative imaging tests.
Conclusions Inadequate fall in intraoperative PTH may be false negative, particularly after removal of an adenoma found in the location
determined by preoperative imaging. Repeat PTH may confirm the initial assay as false negative, obviating the need for additional
neck dissection. Importantly, if repeat PTH does not fall appropriately, additional neck exploration needs to be performed.
Some of the results reported here were part of an oral presentation at the 88th Annual Meeting of the New England Surgical
Society, Burlington, VT, September 29, 2007. 相似文献
78.
Cunha BA Eisenstein LE Dillard T Krol V 《Heart & lung : the journal of critical care》2007,36(1):72-78
Organ transplants are frequently complicated by viral infections. The period of maximum immunosuppression, 1 to 6 months posttransplantation, predisposes one to intracellular pathogens. The most common intracellular viral pathogens in transplant recipients include cytomegalovirus (CMV), herpes simplex virus (HSV), and respiratory syncytial virus (RSV). Cytomegalovirus and HSV are common viral pathogens in the early transplant period (0-1 month posttransplant). Although respiratory syncytial virus commonly presents in the late posttransplant period (> or =6 months posttransplant), HSV pneumonia may be acquired in organ transplants by endogenous reactivation caused by immunosuppression or may be introduced from colonized oropharyngeal secretions into the lower respiratory tract during intubation in patients on ventilators. In ventilated patients without severe preexisting lung disease, HSV pneumonia presents with otherwise unexplained profound/prolonged hypoxemia or "failure to wean." As other viral pneumonias, HSV pneumonia is characterized by profound hypoxemia requiring a high FIo(2), and a highly increased A-a gradient (> or =30). These findings are indicative of an oxygen diffusion defect typical of noninfectious (eg, sarcoidosis) or infectious disorders (eg, HSV, cytomegalovirus, respiratory syncytial virus, Pneumocystis (carinii) jiroveci pneumonia) primarily affecting the interstitium of the lung. We present a case of HSV pneumonia in a heart transplant recipient and include a review of the clinical presentation, diagnostic findings, and therapy of HSV pneumonia. 相似文献
79.
Chronic bacterial infection and severe, polymorphonuclear neutrophil-dominated endobronchial inflammation are characteristic hallmarks of cystic fibrosis (CF) lung disease. The free radicals generated can be deleterious for structure and function of many proteins. The goal of this study was to investigate the degree of oxidation of pulmonary epithelial lining fluid proteins. BAL fluid (BALF) from 55 children with CF and from 11 patients in a control group were investigated by dot-blot assay for content and by two-dimensional electrophoresis and Western blotting for the pattern of distribution of oxidized proteins. The highest level of oxidative stress, as assessed by the level of protein carbonyls, was found in patients with FEV1 < 80% of predicted or with highly elevated neutrophil counts. Compared to control subjects without lung disease, CF patients with normal lung function and CF patients with a normal neutrophil count in their BALF had significantly higher protein carbonyl levels. The extent of protein oxidation was directly related to the neutrophil granulocyte count and inversely to lung function. Our data support the hypothesis that oxidative damage of pulmonary proteins during chronic and excessive neutrophilic endobronchial inflammation may contribute to the decline of lung function in CF patients. 相似文献
80.
Eugenia Stepanova Wilfried Karmaus Marina Naboka Vitaliy Vdovenko Tim Mousseau Viacheslav M Shestopalov John Vena Erik Svendsen Dwight Underhill Harris Pastides 《Environmental health : a global access science source》2008,7(1):21