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Villenave R Thavagnanam S Sarlang S Parker J Douglas I Skibinski G Heaney LG McKaigue JP Coyle PV Shields MD Power UF 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(13):5040-5045
Respiratory syncytial virus (RSV) is the major viral cause of severe pulmonary disease in young infants worldwide. However, the mechanisms by which RSV causes disease in humans remain poorly understood. To help bridge this gap, we developed an ex vivo/in vitro model of RSV infection based on well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs), the primary targets of RSV infection in vivo. Our RSV/WD-PBEC model demonstrated remarkable similarities to hallmarks of RSV infection in infant lungs. These hallmarks included restriction of infection to noncontiguous or small clumps of apical ciliated and occasional nonciliated epithelial cells, apoptosis and sloughing of apical epithelial cells, occasional syncytium formation, goblet cell hyperplasia/metaplasia, and mucus hypersecretion. RSV was shed exclusively from the apical surface at titers consistent with those in airway aspirates from hospitalized infants. Furthermore, secretion of proinflammatory chemokines such as CXCL10, CCL5, IL-6, and CXCL8 reflected those chemokines present in airway aspirates. Interestingly, a recent RSV clinical isolate induced more cytopathogenesis than the prototypic A2 strain. Our findings indicate that this RSV/WD-PBEC model provides an authentic surrogate for RSV infection of airway epithelium in vivo. As such, this model may provide insights into RSV pathogenesis in humans that ultimately lead to successful RSV vaccines or therapeutics. 相似文献
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Porrata LF Ristow K Habermann TM Witzig TE Colgan JP Inwards DJ Ansell SM Micallef IN Johnston PB Nowakowski GS Thompson C Markovic SN 《British journal of haematology》2012,157(3):321-330
The pathological background in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) consists of lymphocytes and histocytes. This study analysed the peripheral blood absolute lymphocyte count/absolute monocyte count ratio at diagnosis (ALC/AMC-DX) on the impact of survival in NLPHL. One hundred and three consecutive NLPHL patients that were followed at Mayo Clinic from 1974 to 2010 were included in the study. Receiver operating characteristic and area under the curve were used for ALC/AMC-DX cut-off value analysis and proportional-hazards models were used to compare survival based on the ALC/AMC-DX ratio. With a median follow-up of 8·9 years (range: 0·3-31 years), an ALC/AMC-DX ≥2·1 was the best cut-off value for survival with an area under the curve of 0·82, a sensitivity of 70% and specificity of 84%. After adjusting for the International Prognostic Score (IPS), ALC/AMC-DX remained an independent prognostic factor for overall survival [Hazard Ratio (HR), 0·33, 95% confidence interval (CI), 0·15-0·71%, P < 0·004]; lymphoma-specific survival (HR, 0·05; 95%CI, 0·01-0·68%, P < 0·002); progression-free survival (HR, 0·30; 95%CI, 0·14-0·60%, P < 0·006), and time to progression (HR, 0·06, 95%CI, 0·04-0·30%, P < 0·004). ALC/AMC-DX is a low cost, already standarized, biomarker to predict clinical outcomes in NLPHL. 相似文献
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Ma?gorzata Waszak Krystyna Cie?lik Karolina Wielgus Ryszard S?omski Marlena Szalata Marzena Skrzypczak-Zielińska Joanna Kempiak Grzegorz Br?borowicz 《Archives of Medical Science》2013,9(6):1102-1106
Introduction
The aim of this paper was to report the occurrence of peripheral blood chimerism in newborns from bigeminal pregnancies.Material and methods
Cord blood collected from 50 pairs of twins constituted the biological material studied. Analyses included: DNA isolation, quantitative and qualitative assessment of DNA preparations, hybridization analysis of SLS type as well as of MLS type, and analysis of microsatellite sequences with regard to polymorphisms using polymerase chain reaction.Results
The presence of additional fragments of DNA in peripheral blood lymphocytes was found in four out of fifty pairs of monozygotic twins (8%) at locus D7S21 (7p22, n = 3) and locus D12S11 (12q24.3, n = 1). In these cases, the presence of additional DNA fragments was also proved by analysis of microsatellite sequence polymorphisms at loci HUMPLA2A1 (pancreatic phospholipase A-2, 12q23), HUMCYARO (cytochrome P450, 15q21.1) and HUMvWF (von Willebrand factor, 12p13).Conclusions
The results of our study confirm the occurrence of chimerism in twins and constitutes the starting point for further studies aimed at determining the clinical significance of chimerism in twins both for women and fetuses. 相似文献80.
Monika Rac Grzegorz Kurzawski Krzysztof Safranow Michal Rac Dagmara Sagasz-Tysiewicz Andrzej Krzystolik Wojciech Poncyljusz Maria Olszewska Gra?yna Dawid Dariusz Chlubek 《Archives of Medical Science》2013,9(4):640-650