510 research outputs found
A silent gigantic solitary fibrous tumor of the pleura: case report
Solitary fibrous tumor of the pleura is a rare mesenchymal tumor, representing less than 5% of all neoplasms associated with the pleura. A 57-year-old man had general malaise without chest symptoms for 1 month. A chest roentgenogram and computed tomography showed a giant mass in the left thorax. Although the tumor compressed the descending aorta and other mediastinal structures strongly, thereby shifting them to the right side, the patient had no symptoms except malaise. The tumor was successfully resected via two separate thoracotomies. The tumor was measured (20 cm × 19 cm × 15 cm) and weighed (2150 g). The tumor was histologically and immunohistochemically diagnosed as benign. Although SFT is benign, a long follow-up period is essential as even patients with complete resection are at risk of recurrence many years after surgery
RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma
© 2017, eLife Sciences Publications Ltd. All rights reserved. Asthma is a chronic inflammatory disease. Although many patients with asthma develop type-2 dominated eosinophilic inflammation, a number of individuals develop paucigranulocytic asthma, which occurs in the absence of eosinophilia or neutrophilia. The aetiology of paucigranulocytic asthma is unknown. However, both respiratory syncytial virus (RSV) infection and mutations in the receptor for advanced glycation endproducts (RAGE) are risk factors for asthma development. Here, we show that RAGE deficiency impairs anti-viral immunity during an early-life infection with pneumonia virus of mice (PVM; a murine analogue of RSV). The elevated viral load was associated with the release of high mobility group box-1 (HMGB1) which triggered airway smooth muscle remodelling in early-life. Re-infection with PVM in later-life induced many of the cardinal features of asthma in the absence of eosinophilic or neutrophilic inflammation. Anti-HMGB1 mitigated both early-life viral disease and asthma-like features, highlighting HMGB1 as a possible novel therapeutic target
Recycled gabbro signature in hotspot magmas unveiled by plume–ridge interactions
Lavas erupted within plate interiors above upwelling mantle
plumes have chemical signatures that are distinct from midocean
ridge lavas. When a plume interacts with a mid-ocean
ridge, the compositions of both their lavas changes, but there
is no consensus as to how this interaction occurs1–3. For the
past 15 Myr, the Pacific–Antarctic mid-ocean ridge has been
approaching the Foundation hotspot4 and erupted lavas have
formed seamounts. Here we analyse the noble gas isotope
and trace element signature of lava samples collected from
the seamounts. We find that both intraplate and on-axis
lavas have noble gas isotope signatures consistent with the
contribution from a primitive plume source. In contrast, nearaxis
lavas show no primitive noble gas isotope signatures, but
are enriched in strontium and lead, indicative of subducted
former oceanic lower crust melting within the plume source5–7.
We propose that, in a near-ridge setting, primitive, plumesourced
magmas formed deep in the plume are preferentially
channelled to and erupted at the ridge-axis. The remaining
residue continues to rise and melt, forming the near-axis
seamounts. With the deep melts removed, the geochemical
signature of subduction contained within the residue becomes
apparent. Lavas with strontium and lead enrichments are found
worldwide where plumes meet mid-ocean ridges6–8, suggesting
that subducted lower crust is an important but previously
unrecognised plume component
Giant Solitary Fibrous Tumor of the Pleura: An Analysis of Five Patients
Ó The Author(s) 2010. This article is published with open access at Springerlink.com Background Solitary fibrous tumor of the pleura (SFTP) represents a clinical entity rarely encountered, especially in giant forms. Complete surgical resection for giant tumor of pleura is a challenge. The aim of this article is to present five new cases of giant SFTP, and to discuss their clinical characteristics and the treatment strategy of such neoplasms. Methods We performed a retrospective review of the clinical records of five patients who underwent surgery for a huge SFTP ([18 cm in diameter) between 2007 and 2009. Results Four patients were symptomatic. All five patients underwent angiography and embolization of the tumorsupplying vessels within 24 h of surgery. All giant tumors were removed completely by extended postlateral thoracotomy with moderate intraoperative bleeding. Two wedge resections and one lobectomy were performed in three cases where the parenchyma had been encroached. Tumors in three patients were pathologically benign; those in the other two were malignant. The symptoms disappeared in all cases after surgery. Conclusions Complete resection remains the mainstay of cure for giant SFTP. We recommend preoperative angiography and embolization for giant SFTP which can reduce the risk of hemorrhage and can contribute to piecemeal removal for radical excision
Isolation and characterisation of human gingival margin-derived STRO-1/MACS+ and MACS− cell populations
Recently, gingival margin-derived stem/progenitor cells isolated via
STRO-1/magnetic activated cell sorting (MACS) showed remarkable periodontal
regenerative potential in vivo. As a second-stage investigation, the present
study's aim was to perform in vitro characterisation and comparison of the
stem/progenitor cell characteristics of sorted STRO-1-positive (MACS+) and
STRO-1-negative (MACS−) cell populations from the human free gingival margin.
Cells were isolated from the free gingiva using a minimally invasive technique
and were magnetically sorted using anti-STRO-1 antibodies. Subsequently, the
MACS+ and MACS− cell fractions were characterized by flow cytometry for
expression of CD14, CD34, CD45, CD73, CD90, CD105, CD146/MUC18 and STRO-1.
Colony-forming unit (CFU) and multilineage differentiation potential were
assayed for both cell fractions. Mineralisation marker expression was examined
using real-time polymerase chain reaction (PCR). MACS+ and MACS− cell
fractions showed plastic adherence. MACS+ cells, in contrast to MACS− cells,
showed all of the predefined mesenchymal stem/progenitor cell characteristics
and a significantly higher number of CFUs (P<0.01). More than 95% of MACS+
cells expressed CD105, CD90 and CD73; lacked the haematopoietic markers CD45,
CD34 and CD14, and expressed STRO-1 and CD146/MUC18. MACS− cells showed a
different surface marker expression profile, with almost no expression of CD14
or STRO-1, and more than 95% of these cells expressed CD73, CD90 and
CD146/MUC18, as well as the haematopoietic markers CD34 and CD45 and CD105.
MACS+ cells could be differentiated along osteoblastic, adipocytic and
chondroblastic lineages. In contrast, MACS− cells demonstrated slight
osteogenic potential. Unstimulated MACS+ cells showed significantly higher
expression of collagen I (P<0.05) and collagen III (P<0.01), whereas MACS−
cells demonstrated higher expression of osteonectin (P<0.05; Mann–Whitney).
The present study is the first to compare gingival MACS+ and MACS− cell
populations demonstrating that MACS+ cells, in contrast to MACS− cells,
harbour stem/progenitor cell characteristics. This study also validates the
effectiveness of the STRO-1/MACS+ technique for the isolation of gingival
stem/progenitor cells. Human free gingival margin-derived STRO-1/MACS+ cells
are a unique renewable source of multipotent stem/progenitor cells
Asynchronous Antarctic and Greenland ice-volume contributions to the last interglacial sea-level highstand
The last interglacial (LIG; ~130 to ~118 thousand years ago, ka) was the last time global sea level rose well above the present level. Greenland Ice Sheet (GrIS) contributions were insufficient to explain the highstand, so that substantial Antarctic Ice Sheet (AIS) reduction is implied. However, the nature and drivers of GrIS and AIS reductions remain enigmatic, even though they may be critical for understanding future sea-level rise. Here we complement existing records with new data, and reveal that the LIG contained an AIS-derived highstand from ~129.5 to ~125 ka, a lowstand centred on 125–124 ka, and joint AIS + GrIS contributions from ~123.5 to ~118 ka. Moreover, a dual substructure within the first highstand suggests temporal variability in the AIS contributions. Implied rates of sea-level rise are high (up to several meters per century; m c−1), and lend credibility to high rates inferred by ice modelling under certain ice-shelf instability parameterisations
PPAR-γ Ligands Repress TGFβ-Induced Myofibroblast Differentiation by Targeting the PI3K/Akt Pathway: Implications for Therapy of Fibrosis
Transforming growth factor beta (TGFβ) induced differentiation of human lung fibroblasts to myofibroblasts is a key event in the pathogenesis of pulmonary fibrosis. Although the typical TGFβ signaling pathway involves the Smad family of transcription factors, we have previously reported that peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands inhibit TGFβ-mediated differentiation of human lung fibroblasts to myofibroblasts via a Smad-independent pathway. TGFβ also activates the phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) pathway leading to phosphorylation of AktS473. Here, we report that PPAR-γ ligands, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) and 15-deoxy-(12,14)-15d-prostaglandin J2 (15d-PGJ2), inhibit human myofibroblast differentiation of normal and idiopathic pulmonary fibrotic (IPF) fibroblasts, by blocking Akt phosphorylation at Ser473 by a PPAR-γ-independent mechanism. The PI3K inhibitor LY294002 and a dominant-negative inactive kinase-domain mutant of Akt both inhibited TGFβ-stimulated myofibroblast differentiation, as determined by Western blotting for α-smooth muscle actin and calponin. Prostaglandin A1 (PGA1), a structural analogue of 15d-PGJ2 with an electrophilic center, also reduced TGFβ-driven phosphorylation of Akt, while CAY10410, another analogue that lacks an electrophilic center, did not; implying that the activity of 15d-PGJ2 and CDDO is dependent on their electrophilic properties. PPAR-γ ligands inhibited TGFβ-induced Akt phosphorylation via both post-translational and post-transcriptional mechanisms. This inhibition is independent of MAPK-p38 and PTEN but is dependent on TGFβ-induced phosphorylation of FAK, a kinase that acts upstream of Akt. Thus, PPAR-γ ligands inhibit TGFβ signaling by affecting two pro-survival pathways that culminate in myofibroblast differentiation. Further studies of PPAR-γ ligands and small electrophilic molecules may lead to a new generation of anti-fibrotic therapeutics
Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector
Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente
Correlates of women's cancer screening and contraceptive knowledge among female emergency department patients
<p>Abstract</p> <p>Background</p> <p>Lack of knowledge regarding preventive health services for women might impede campaigns to expand these services in the emergency department setting. For 18–55-year-old English-speaking women visiting an urban emergency department, we aimed to: (1) Ascertain their knowledge regarding the applicability, purpose, and recommended intervals of three women's cancer screening and three contraceptive methods; and (2) Determine if patient age, race/ethnicity, medical insurance status, and current or recent usage of these methods are associated with greater or lesser knowledge about them.</p> <p>Methods</p> <p>Emergency department-based survey on recent or current usage and knowledge about Pap smears, breast self-examinations, mammograms, condoms, birth control, and emergency contraception. Analyses included calculation of summary statistics and creation of multivariable logistic regression models.</p> <p>Results</p> <p>Of 1,100 patients eligible for the study, 69.9% agreed to participate. Most of the participants were < age 35, white, single (never married and no partner), Catholic, and had private medical insurance. Participant's recent or current usage of a particular cancer screening or contraceptive method varied by type of method: Pap smear within the past year (69.1%), breast self-exam within the past month (45.5%), mammogram within the past year (65.7% for women age 45–55), condom usage during every episode of sexual intercourse (15.4%), current usage of birth control pills (17.8%), and ever use of emergency contraception (9.3%). The participants correctly answered 87.9% of all survey questions about condoms, 82.5% about birth control pills, 78.5% about breast self-exams, 52.9% about Pap smears, 35.4% about mammograms, and 25.0% about emergency contraception. In multivariable logistic regression models, survey participants who had private medical insurance and those who recently or currently used a given screening or contraceptive method had a greater odds of correctly answering all questions about each cancer screening or contraceptive method.</p> <p>Conclusion</p> <p>Although these female ED patients demonstrated strong knowledge on some women's cancer screening and contraceptive methods, there were several areas of knowledge deficit. Women without private medical insurance and those who have not used a particular cancer screening or contraceptive method demonstrated less knowledge. Reduced knowledge about women's cancer screening and contraceptive methods should be considered during clinical encounters and when instituting or evaluating emergency department-based initiatives that assess the need for these methods.</p
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