bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Prototype Foamy Virus particle-host cell interaction with autofluorescent retroviral particles
Authors: Stirnnagel Kristin , Lüftenegger Daniel , Stange Annett , Swiersy Anka , Müllers Erik , Reh Juliane , Stanke Nicole , Große Arend , Chiantia Salvatore , Keller Heiko , Schwille Petra , Hanenberg Helmut , Zentgraf Hanswalter , Lindemann Dirk 
Published: May 2010

Abstract

Background
The foamy virus (FV) replication cycle displays several unique features, which set them apart from orthoretroviruses. First, like other B/D type orthoretroviruses, FV capsids preassemble at the centrosome, but more similar to hepadnaviruses, FV budding is strictly dependent on cognate viral glycoprotein coexpression. Second, the unusually broad host range of FV is thought to be due to use of a very common entry receptor present on host cell plasma membranes, because all cell lines tested in vitro so far are permissive.

Results
In order to take advantage of modern fluorescent microscopy techniques to study FV replication, we have created FV Gag proteins bearing a variety of protein tags and evaluated these for their ability to support various steps of FV replication. Addition of even small N-terminal HA-tags to FV Gag severely impaired FV particle release. For example, release was completely abrogated by an N-terminal autofluorescent protein (AFP) fusion, despite apparently normal intracellular capsid assembly. In contrast, C-terminal Gag-tags had only minor effects on particle assembly, egress and particle morphogenesis. The infectivity of C-terminal capsid-tagged FV vector particles was reduced up to 100-fold in comparison to wild type; however, infectivity was rescued by coexpression of wild type Gag and assembly of mixed particles. Specific dose-dependent binding of fluorescent FV particles to target cells was demonstrated in an Env-dependent manner, but not binding to target cell-extracted- or synthetic- lipids. Screening of target cells of various origins resulted in the identification of two cell lines, a human erythroid precursor- and a zebrafish- cell line, resistant to FV Env-mediated FV- and HIV-vector transduction.

Conclusions
We have established functional, autofluorescent foamy viral particles as a valuable new tool to study FV - host cell interactions using modern fluorescent imaging techniques. Furthermore, we succeeded for the first time in identifying two cell lines resistant to Prototype Foamy Virus Env-mediated gene transfer. Interestingly, both cell lines still displayed FV Env-dependent attachment of fluorescent retroviral particles, implying a post-binding block potentially due to lack of putative FV entry cofactors. These cell lines might ultimately lead to the identification of the currently unknown ubiquitous cellular entry receptor(s) of FVs.
Merotelic attachments and non-homologous end joining are the basis of chromosomal instability
Authors: Guerrero Astrid Alonso , Martínez-A Carlos , van Wely Karel HM 
Published: May 2010

Abstract
Although the large majority of solid tumors show a combination of mitotic spindle defects and chromosomal instability, little is known about the mechanisms that govern the initial steps in tumorigenesis. The recent report of spindle-induced DNA damage provides evidence for a single mechanism responsible for the most prominent genetic defects in chromosomal instability. Spindle-induced DNA damage is brought about by uncorrected merotelic attachments, which cause kinetochore distortion, chromosome breakage at the centromere, and possible activation of DNA damage repair pathways. Although merotelic attachments are common early in mitosis, some escape detection by the kinetochore pathway. As a consequence, a proportion of merotelic attachments gives rise to chromosome breakage in normal cells and in carcinomas. An intrinsic chromosome segregation defect might thus form the basis of tumor initiation. We propose a hypothesis in which merotelic attachments and chromosome breakage establish a feedback loop that results in relaxation of the spindle checkpoint and suppression of anti-proliferative pathways, thereby promoting carcinogenesis.
Multislice computed tomography is useful for evaluating partial anomalous pulmonary venous connection
Authors: Kasahara Hirofumi , Aeba Ryo , Tanami Yutaka , Yozu Ryohei 
Published: May 2010

Abstract
Volume-rendered images, derived from multidetector-row computed tomography (MDCT), can facilitate assessment of the morphology of partial anomalous pulmonary venous connection and are thus useful in pre-operative planning to prevent surgical morbidity and assist post-operative evaluations.
The roles of p38MAPK and caspase-3 in DADS-induced apoptosis in human HepG2 cells
Authors: Ji Chunxiao , Ren Fenglian , Ma Heng , Xu Ming 
Published: May 2010

AbstractObjectivesTo explore the function of p38MAPK and caspase-3 in DADS-induced apoptosis in human HepG2 cells, and discuss the signal transduetion mechanism of HepG2 cells in the apoptosis process induced by DADS by using the inhibitors of p38MAPK (SB203580) and caspase-3 (Z-DEVD-FMK).MethodsAfter the human HepG2 cells had been treated with the DADS and inhibitors for 24 h, cell viability was determined by the MTT method, apoptosis was evaluated by flow cytometry (FCM) and the expressions of p38MAPK and caspase-3 were measured by western-blot.ResultsOur results indicated that DADS activities the p38MAPK and caspase-3, but the inhibitors, SB203580 and Z-DEVD-FMK (for p38MAPKand for caspase-3, respectively), both have the effect of inhibitory activity on P38MAPK and caspase-3. Furthermore, a combination treatment with both DADS and inhibitor (SB203580 or Z-DEVD-FMK) decreases the inhibitory and apoptotic activity of HepG2 cells increased compared with DADS-treated.ConclusionsOur data indicate that p38MAPK and caspase-3 are involved in the process of DADS-induced apoptosis in human HepG2 cells and interact with each other.
Experimental stress in inflammatory rheumatic diseases: a review of psychophysiological stress responses
Authors: de Brouwer Sabine JM , Kraaimaat Floris W , Sweep Fred CGJ , Creemers Marjonne CW , Radstake Timothy RDJ , van Laarhoven Antoinette IM , van Riel Piet LCM , Evers Andrea WM 
Published: May 2010

AbstractIntroductionStressful events are thought to contribute to the aetiology, maintenance and exacerbation of rheumatic diseases. Given the growing interest in acute stress responses and disease, this review investigates the impact of real-life experimental psychosocial, cognitive, exercise and sensory stressors on autonomic, neuroendocrine and immune function in patients with inflammatory rheumatic diseases.MethodsDatabases Medline, PsychINFO, Embase, Cinahl and Pubmed were screened for studies (1985 to 2009) investigating physiological stress responses in inflammatory rheumatic diseases. Eighteen articles met the inclusion criteria.ResultsResults suggest that immune function may be altered in response to a stressor; such alterations could contribute to the maintenance or exacerbation of inflammatory rheumatic diseases during stressful events in daily life.ConclusionsThis review emphasizes the need for more experimental research in rheumatic populations with controlled stress paradigms that include a follow-up with multiple evaluation points, simultaneous assessment of different physiological stress systems, and studying factors contributing to specific physiological responses, such as stress appraisal.
Monocyte surface expression of Fcγ receptor RI (CD64), a biomarker reflecting type-I interferon levels in systemic lupus erythematosus
Authors: Li Yi , Lee Pui Y , Kellner Erinn S , Paulus Matthew , Switanek Juliana , Xu Yuan , Zhuang Haoyang , Sobel Eric S , Segal Mark S , Satoh Minoru , Reeves Westley H 
Published: May 2010

Abstract
Introduction
More than half of systemic lupus erythematosus (SLE) patients show evidence of excess type I interferon (IFN-I) production, a phenotype associated with renal disease and certain autoantibodies. However, detection of IFN-I proteins in serum is unreliable, and the measurement of interferon-stimulated gene (ISG) expression is expensive and time consuming. The aim of this study was to identify a surrogate marker for IFN-I activity in clinical samples for monitoring disease activity and response to therapy.

Methods
Monocyte surface expression of Fcγ receptors (FcγRs), chemokine receptors, and activation markers were analyzed with flow cytometry in whole blood from patients with SLE and healthy controls. FcγR expression also was measured in peripheral blood mononuclear cells (PBMCs) from healthy controls cultured with Toll-like receptor (TLR) agonists, cytokines, or serum from SLE patients. Expression of ISGs was analyzed with real-time PCR.

Results
Circulating CD14+ monocytes from SLE patients showed increased surface expression of FcγRI (CD64). The mean fluorescent intensity of CD64 staining correlated highly with the ISG expression (MX1, IFI44, and Ly6E). In vitro, IFN-I as well as TLR7 and TLR9 agonists, induced CD64 expression on monocytes from healthy controls. Exposure of monocytes from healthy controls to SLE sera also upregulated the expression of CD64 in an IFN-I-dependent manner. Decreased CD64 expression was observed concomitant with the reduction of ISG expression after high-dose corticosteroid therapy.

Conclusions
Expression of CD64 on circulating monocytes is IFN-I inducible and highly correlated with ISG expression. Flow-cytometry analysis of CD64 expression on circulating monocytes is a convenient and rapid approach for estimating IFN-I levels in SLE patients.
Phenotypic and functional abnormalities of bone marrow-derived dendritic cells in systemic lupus erythematosus
Authors: Nie Ying J , Mok Mo Y , Chan Godfrey CF , Chan Albert W , Jin Ou , Kavikondala Sushma , Lie Albert KW , Lau Chak S 
Published: May 2010

Abstract
Introduction
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoreactive T and B cells, which are believed to be secondary to deficient dendritic cells (DCs). However, whether DC abnormalities occur during their development in the bone marrow (BM) or in the periphery is not known.

Methods
Thirteen patients with SLE and 16 normal controls were recruited. We studied the morphology, phenotype, and functional abilities of bone marrow-derived dendritic cells (BMDCs) generated by using two culture methods: FMS-like tyrosine kinase 3 (Flt3)-ligand (FL) and granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4), respectively.

Results
BMDCs induced by FL exhibited both myeloid (mDC) and plasmacytoid DC (pDC) features, whereas GM-CSF/IL-4 induced mDC generation. Substantial phenotypic and functional defects of BMDCs were found from patients with SLE at different stages of cell maturation. When compared with healthy controls, SLE immature BM FLDCs expressed higher levels of CCR7. Both immature and mature SLE BM FLDCs expressed higher levels of CD40 and CD86 and induced stronger T-cell proliferation. SLE BM mDCs expressed higher levels of CD40 and CD86 but lower levels of HLA-DR and a lower ability to stimulate T-cell proliferation when compared with control BM mDCs.

Conclusions
Our data are in accordance with previous reports that suggest that DCs have a potential pathogenic role in SLE. Defects of these cells are evident during their development in BM. BM mDCs are deficient, whereas BM pDCs, which are part of BM FLDCs, are the likely culprit in inducing autoimmunity in SLE.
Treatment with apolipoprotein A-1 mimetic peptide reduces lupus-like manifestations in a murine lupus model of accelerated atherosclerosis
Authors: Woo Jennifer MP , Lin Zhuofeng , Navab Mohamad , Van Dyck Casey , Trejo-Lopez Yvette , Woo Krystal MT , Li Hongyun , Castellani Lawrence W , Wang Xuping , Iikuni Noriko , Rullo Ornella J , Wu Hui , La Cava Antonio , Fogelman Alan M , Lusis Aldons J , Tsao Betty P 
Published: May 2010

AbstractIntroductionThe purpose of this study was to evaluate the effects of L-4F, an apolipoprotein A-1 mimetic peptide, alone or with pravastatin, in apoE-/-Fas-/-C57BL/6 mice that spontaneously develop immunoglobulin G (IgG) autoantibodies, glomerulonephritis, osteopenia, and atherosclerotic lesions on a normal chow diet.MethodsFemale mice, starting at eight to nine weeks of age, were treated for 27 weeks with 1) pravastatin, 2) L-4F, 3) L-4F plus pravastatin, or 4) vehicle control, followed by disease phenotype assessment.ResultsIn preliminary studies, dysfunctional, proinflammatory high-density lipoproteins (piHDL) were decreased six hours after a single L-4F, but not scrambled L-4F, injection in eight- to nine-week old mice. After 35 weeks, L-4F-treated mice, in the absence/presence of pravastatin, had significantly smaller lymph nodes and glomerular tufts (PL,LP< 0.05), lower serum levels of IgG antibodies to double stranded DNA (dsDNA) (PL< 0.05) and oxidized phospholipids (oxPLs) (PL,LP< 0.005), and elevated total and vertebral bone mineral density (PL,LP< 0.01) compared to vehicle controls. Although all treatment groups presented larger aortic root lesions compared to vehicle controls, enlarged atheromas in combination treatment mice had significantly less infiltrated CD68+macrophages (PLP< 0.01), significantly increased mean α-actin stained area (PLP< 0.05), and significantly lower levels of circulating markers for atherosclerosis progression, CCL19 (PL,LP< 0.0005) and VCAM-1 (PL< 0.0002).ConclusionsL-4F treatment, alone or with pravastatin, significantly reduced IgG anti-dsDNA and IgG anti-oxPLs, proteinuria, glomerulonephritis, and osteopenia in a murine lupus model of accelerated atherosclerosis. Despite enlarged aortic lesions, increased smooth muscle content, decreased macrophage infiltration, and decreased pro-atherogenic chemokines in L-4F plus pravastatin treated mice suggest protective mechanisms not only on lupus-like disease, but also on potential plaque remodeling in a murine model of systemic lupus erythematosus (SLE) and accelerated atherosclerosis.
Remission in psoriatic arthritis: is it possible and how can it be predicted?
Authors: Saber Tajvur P , Ng CT , Renard Guillaume , Lynch Bernadette M , Pontifex Eliza , Walsh Ceara AE , Grier Alexia , Molloy Marian , Bresnihan Barry , FitzGerald Oliver , Fearon Ursula , Veale Douglas J 
Published: May 2010

Abstract
Introduction
Since remission is now possible in psoriatic arthritis (PsA) we wished to examine remission rates in PsA patients following anti tumour necrosis factor alpha (TNFα) therapy and to examine possible predictors of response.

Methods
Analysis of a prospective patient cohort attending a biologic clinic, between November 2004 and March 2008, was performed prior to commencing therapy and at regular intervals. Baseline clinical characteristics including demographics, previous disease-modifying antirheumatic drug (DMARD) response, tender and swollen joint counts, early morning stiffness, pain visual analogue score, patient global assessment, C reactive protein (CRP) and health assessment questionnaire (HAQ) were collected.

Results
A total of 473 patients (152 PsA; 321 rheumatoid arthritis (RA)) were analyzed. At 12 months remission, defined according to the disease activity score using 28 joint count and CRP (DAS28-CRP), was achieved in 58% of PsA patients compared to 44% of RA patients, significant improvement in outcome measures were noted in both groups (P < 0.05). Analysis of a subgroup of PsA and RA patients matched for DAS28-CRP at baseline also showed higher numbers of PsA patients achieving remission. Linear regression analysis identified the HAQ at baseline as the best predictor of remission in PsA patients (P < 0.001).

Conclusions
DAS28 remission is possible in PsA patients at one year following anti-TNF therapy, at higher rates than in RA patients and is predicted by baseline HAQ.
Angiopoietin-2 is increased in sepsis and inversely associated with nitric oxide-dependent microvascular reactivity
Authors: Davis Joshua S , Yeo Tsin W , Piera Kim A , Woodberry Tonia , Celermajer David S , Stephens Dianne P , Anstey Nicholas M 
Published: May 2010

Abstract
Introduction
Angiopoietin-2 (ang-2), an angiogenic peptide released by endothelial cell Weibel-Palade bodies (WPBs), increases endothelial activation and vascular permeability. Ang-2 is raised in severe sepsis but the mechanisms underlying this are not known. Nitric oxide (NO) inhibits WPB exocytosis, and bioavailability of endothelial NO is decreased in sepsis. We hypothesized that endothelial NO bioavailability would be inversely correlated with ang-2 concentrations in sepsis.

Methods
Plasma ang-2, vascular endothelial growth factor (VEGF) and endothelial-active cytokines were assessed in 83 patients with early sepsis and 41 hospital controls, and related to reactive hyperaemia-peripheral arterial tonometry, RH-PAT, a measure of endothelial NO bioavailability.

Results
Plasma Ang-2 was elevated in sepsis (median [interquartile range (IQR)], ng/ml: severe sepsis 12.4 [8.5-33.4], sepsis without organ failure 6.1 [5.0-10.4], controls 2.7 [2.2-3.6], P < 0.0001). It correlated inversely with RH-PAT (r = -0.38, P < 0.0001) and positively with IL-6 (r = 0.57, P < 0.0001) and degree of organ failure (sequential organ function assessment score) (r = 0.58, P < 0.0001). The correlation of ang-2 with RH-PAT persisted after controlling for sepsis severity. In a longitudinal mixed-effects model, recovery of RH-PAT over time was associated with decline in ang-2.

Conclusions
Ang-2 is elevated in proportion to sepsis severity, and inversely correlated with NO-dependent microvascular reactivity. Impaired endothelial NO bioavailability may contribute to increased endothelial cell release of ang-2, endothelial activation and capillary leak. Agents that increase endothelial NO bioavailability or inhibit WPB exocytosis and/or Ang-2 activity may have therapeutic potential in sepsis.
Effective Reduction of Gastric Cancer Risk With Regular Use of Nonsteroidal Anti-Inflammatory Drugs in Helicobacter Pylori–Infected Patients
Authors: Wu Chun-Ying , Wu Ming-Shiang , Kuo Ken N. , Wang Chang-Bi , Chen Yi-Ju , Lin Jaw-Town 
Published: May 2010

Purpose Nonsteroidal anti-inflammatory drugs (NSAIDs) play protective roles in gastric carcinogenesis. However, the interaction between NSAIDs and Helicobacter pylori (H pylori) infection and the number needed to treat to prevent gastric cancer remains unclear. Patients and Methods We conducted a nationwide retrospective cohort study based on data from the Taiwan National Health Insurance Database. Hospitalized patients with a primary diagnosis of peptic ulcer disease were selected. Overall, 52,161 patients were divided into non-NSAID user and regular NSAID user cohorts. Standardized incidence ratios (SIRs), cumulative incidences, and hazard ratios (HRs) were calculated. Results Patients with peptic ulcers who never used NSAIDs had higher risk of gastric cancer compared with the general population (SIR, 2.11; 95% CI, 2.07 to 2.15), but regular NSAID use conferred lower risk (SIR, 0.79; 95% CI, 0.77 to 0.81). The protective role of NSAID use was observed in patients with gastric ulcer, but not in patients with non–H pylori-associated duodenal ulcer. On multivariate analysis, regular NSAID use was an independent protective factor for gastric cancer development (HR, 0.79 for each incremental year; P < .001), especially in H pylori-associated patients (HR, 0.52 for each incremental year; P < .001). Among patients with H pylori-infected gastric ulcers, the NNT to prevent a gastric cancer was 50. Conclusion Regular NSAID use may be a feasible way to prevent gastric cancer, at least in patients with gastric ulcers, and especially in H pylori-infected subjects.
Akt Phosphorylation at Ser473 Predicts Benefit of Paclitaxel Chemotherapy in Node-Positive Breast Cancer
Authors: Yang Sherry X. , Costantino Joseph P. , Kim Chungyeul , Mamounas Eleftherios P. , Nguyen Dat , Jeong Jong-Hyeon , Wolmark Norman , Kidwell Kelley , Paik Soonmyung , Swain Sandra M. 
Published: May 2010

Purpose We tested the hypothesis that Akt-Ser473 phosphorylation (pAkt) predicts benefit from the sequential addition of paclitaxel to adjuvant doxorubicin plus cyclophosphamide (AC) chemotherapy in patients with node-positive breast cancer participating in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-28 trial. Patients and Methods Primary tumors from the NSABP B-28 trial tissue microarray were available from 1,581 of 3,060 patients who were randomly assigned to receive either four cycles of AC alone or followed by four cycles of paclitaxel. Immunohistochemistry and quantitative analysis of pAkt were performed at the National Cancer Institute blinded to clinical outcome. Association between pAkt and clinical outcome was assessed using multivariate Cox modeling adjusting for age, tumor size, number of positive nodes, tumor grade, estrogen receptor status, and human epidermal growth factor receptor 2 status. Results With a median follow-up of 9.1 years, there were no differences in disease-free survival (adjusted hazard ratio [HR], 1.02; P = .81) or overall survival (HR, 0.97; P = .80) with and without receiving paclitaxel among 975 patients with pAkt-negative tumors. In 606 patients with pAkt-positive tumors, the sequential addition of paclitaxel resulted in a 26% improvement in disease-free survival (HR, 0.74; P = .02) or a 20% improvement in overall survival (HR, 0.80; P = .17). Conclusion pAkt significantly predicts disease-free benefit from the sequential addition of paclitaxel to AC chemotherapy in patients with node-positive breast cancer. Patients with pAkt-negative breast tumors do not appear to benefit from the addition of paclitaxel.
Longitudinal Study of Depressive Symptoms in Patients With Metastatic Gastrointestinal and Lung Cancer
Authors: Lo Christopher , Zimmermann Camilla , Rydall Anne , Walsh Andrew , Jones Jennifer M. , Moore Malcolm J. , Shepherd Frances A. , Gagliese Lucia , Rodin Gary 
Published: May 2010

Purpose Although early intervention is increasingly advocated to prevent and relieve distress in patients with metastatic cancer, the risk factors for such symptoms and their trajectory are not well established. We therefore conducted a longitudinal study to determine the course and predictors of depressive symptoms. Patients and Methods Patients (N = 365) with metastatic gastrointestinal or lung cancer completed measures of physical distress, self-esteem, attachment security, spiritual well-being, social support, hopelessness, and depression at baseline; physical distress, social support, hopelessness, and depression were subsequently assessed at 2-month intervals. Results Of the sample, 35% reported at least mild depressive symptoms, with 16% reporting moderate to severe depressive symptoms that persisted in at least one third of such individuals. Moderate to severe depressive symptoms were almost three times more common in the final 3 months of life than ≥ 1 year before death. Predictors of depressive symptoms included younger age, antidepressant use at baseline, lower self-esteem and spiritual well-being, and greater attachment anxiety, hopelessness, physical burden of illness, and proximity to death. The combination of greater physical suffering and psychosocial vulnerability put individuals at greatest risk for depression. Conclusion Depressive symptoms in advanced cancer patients are relatively common and may arise as a final common pathway of distress in response to psychosocial vulnerabilities, physical suffering, and proximity to death. These findings support the need for an integrated approach to address emotional and physical distress in this population and to determine whether early intervention may prevent depression at the end of life.