bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening for pulmonary arteriovenous malformations using transthoracic contrast echocardiography: a prospective study
Authors: van Gent M. W. F. , Post M. C. , Luermans J. G. L. M. , Snijder R. J. , Westermann C. J. J. , Plokker H. W. M. , Overtoom T. T. , Mager J. J. 
Published: September 2008

Pulmonary arteriovenous malformations (PAVMs) are associated with severe neurological complications in patients with hereditary haemorrhagic telangiectasia (HHT). The objective of the present study was to prospectively establish the diagnostic value of transthoracic contrast echocardiography (TTCE) as a screening technique for PAVM using chest high-resolution computed tomography (HRCT) as the gold standard for PAVMs.All consecutive adult patients referred for HHT screening underwent a chest HRCT (n = 299), TTCE (n = 281), arterial blood gas analysis (n = 291), shunt fraction measurement (n = 111) and chest radiography (n = 296).TTCE was positive in 87 (58.8%), 12 (16.7%) and four (6.7%) patients, and chest HRCT was positive in 54 (36.5%), three (4.2%) and zero (0%) patients with a definite, possible and negative clinical diagnosis of HHT, respectively. Two patients with a negative TTCE were diagnosed with PAVMs after computed tomography; in both cases the PAVMs were too small to be treated by embolotherapy. The sensitivity of TTCE was 97% (95% confidence interval (CI) 93.6–98.3) and negative predictive value 99% (95% CI 96.9–99.8). The other diagnostic tests showed a considerable lower diagnostic value.The present prospective study shows that transthoracic contrast echocardiography has an excellent diagnostic value and can be used as an initial screening procedure for pulmonary arteriovenous malformations. The high false-positive rate of transthoracic contrast echocardiography possibly represents microscopic pulmonary arteriovenous malformations.
Risk factors for chronic thromboembolic pulmonary hypertension
Authors: Bonderman D. , Wilkens H. , Wakounig S. , Schäfers H-J. , Jansa P. , Lindner J. , Simkova I. , Martischnig A. M. , Dudczak J. , Sadushi R. , Skoro-Sajer N. , Klepetko W. , Lang I. M. 
Published: September 2008

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by nonresolving pulmonary thromboemboli that can be treated by surgical pulmonary endarterectomy (PEA). The authors of the present study sought to confirm known and to identify novel CTEPH risk factors in a controlled retrospective cohort study of prevalent CTEPH cases collected in three European centres offering PEA.Data from CTEPH patients were compared with nonthromboembolic pre-capillary pulmonary arterial hypertension cohorts at the participating institutions.The study population comprised 687 patients assessed at the time of diagnosis between 1996 and 2007. Ventriculo-atrial shunts and infected pacemakers (odds ratio (OR) 76.40, 95% confidence interval (CI) 7.67–10,351), splenectomy (OR 17.87, 95% CI 1.56–2,438), previous venous thromboembolism (VTE; OR 4.52, 95% CI 2.35–9.12), recurrent VTE (OR 14.49, 95% CI 5.40–43.08), blood groups other than 0 (2.09, 95% CI 1.12–3.94), and lupus anticoagulant/antiphospholipid antibodies (OR 4.20, 95% CI 1.56–12.21) were more often associated with CTEPH. Thyroid replacement therapy (OR 6.10, 95% CI 2.73–15.05) and a history of malignancy (OR 3.76, 95% CI 1.47–10.43) emerged as novel CTEPH risk factors.In conclusion, the European database study confirmed previous knowledge of chronic thromboembolic pulmonary hypertension risk factors, and identified thyroid replacement therapy and a history of malignancy as new medical conditions associated with chronic thromboembolic pulmonary hypertension.
Circulating fibronectin to C-reactive protein ratio and mortality: a biomarker in COPD?
Authors: Man S. F. P. , Xing L. , Connett J. E. , Anthonisen N. R. , Wise R. A. , Tashkin D. P. , Zhang X. , Vessey R. , Walker T. G. , Celli B. R. , Sin D. D. 
Published: September 2008

The balance between inflammatory and repair processes is important in maintaining lung homeostasis in chronic obstructive pulmonary disease (COPD). The aim of the present study was to determine whether or not an integrated index of a biomarker involved in inflammation, C-reactive protein (CRP), and another involved in wound repair, fibronectin, may be a good measure to predict clinical outcomes in COPD.Circulating blood levels of CRP and fibronectin were measured in 4,787 individuals with mild-to-moderate COPD who were prospectively followed for >7 yrs after blood collection as part of the Lung Health Study. To assess the balance between repair and inflammation, a simple ratio was calculated by dividing fibronectin levels by CRP levels and a Cox proportional hazards model was used to determine the relationship between this ratio and all-cause and disease-specific causes of mortality.The relationship between the fibronectin to CRP ratio and all-cause mortality was L-shaped. There was an exponential decay in the adjusted hazard function (i.e.the risk of mortality) as the ratio decreased until a value of 148 was reached, beyond which point the hazard function did not change significantly. Similar results were observed for the risk of coronary and cardiovascular mortality.Circulating fibronectin to CRP ratio is significantly associated with all-cause mortality of COPD patients. However, in contrast to other biomarkers, the relationship appears to be L-shaped (and not linear), suggesting a threshold at ∼150. While promising, future studies are needed to validate this simple index as a biomarker in COPD.
Association of mast cells with lung function in chronic obstructive pulmonary disease
Authors: Gosman Margot ME , Postma Dirkje S , Vonk Judith M , Rutgers Bea , Lodewijk Monique , Smith Mieke , Luinge Marjan A , ten Hacken Nick HT , Timens Wim 
Published: September 2008

AbstractBackgroundIn asthma, higher chymase positive mast cell (MC-C) numbers are associated with less airway obstruction. In COPD, the distribution of MC-C and tryptase positive mast cells (MC-T) in central and peripheral airways, and their relation with lung function, is unknown. We compared MC-T and MC-C distributions in COPD and controls without airflow limitation, and determined their relation with lung function.MethodsLung tissue sections from 19 COPD patients (median [interquartile range] FEV1% predicted 56 [23–75]) and 10 controls were stained for tryptase and chymase. Numbers of MC-T and MC-C were determined in different regions of central and peripheral airways and percentage of degranulation was determined.ResultsCOPD patients had lower MC-T numbers in the subepithelial area of central airways than controls. In COPD, MC-T numbers in the airway wall and more specifically in the epithelium and subepithelial area of peripheral airways correlated positively with FEV1/VC (Spearman's rho (rs) 0.47, p = 0.05 and rs0.48, p = 0.05, respectively); MC-C numbers in airway smooth muscle of peripheral airways correlated positively with FEV1% predicted (rs0.57, p = 0.02). Both in COPD patients and controls the percentage of degranulated MC-T and MC-C mast cells was higher in peripheral than in central airways (all p < 0.05), but this was not different between the groups.ConclusionMore MC-T and MC-C in peripheral airways correlate with better lung function in COPD patients. It is yet to determine whether this reflects a protective association of mast cells with COPD pathogenesis, or that other explanations are to be considered.
Establishment and characterization of immortalized Gli-null mouse embryonic fibroblast cell lines
Authors: Lipinski Robert J , Bijlsma Maarten F , Gipp Jerry J , Podhaizer David J , Bushman Wade 
Published: September 2008

Abstract

Background
Hedgehog (Hh) signaling is a conserved morphogenetic pathway which plays critical roles in embryonic development, with emerging evidence also supporting a role in healing and repair processes and tumorigenesis. The Gli family of transcription factors (Gli1, 2 and 3) mediate the Hedgehog morphogenetic signal by regulating the expression of downstream target genes. We previously characterized the individual and cooperative roles of the Gli proteins in Hh target gene regulation using a battery of primary embryonic fibroblasts from Gli null mice.

Results
Here, we describe the establishment of spontaneously immortalized mouse embryonic fibroblast (iMEF) cell lines lacking single and multiple Gli genes. These non-clonal cell lines recapitulate the unique ligand mediated transcriptional response of primary MEFs. While loss of Gli1 had no effect on target gene induction, Gli2 null cells demonstrated reduced target gene induction while Gli3 null cells exhibited elevated basal and ligand-induced expression. Target gene response in Gli1
-/-
2
-/- iMEFs was severely reduced while Gli2
-/-
3
-/- iMEFs were incapable of ligand-induced transcriptional response. However, we found that both Gli1
-/-
2
-/- and Gli2
-/-
3
-/- iMEFs exhibited robust leukotriene synthesis-dependent migration responses to Hh ligand, demonstrating that this response is not transcriptionally-dependent.

Conclusion
This study provides fundamental characterizations of the transcriptional and non-transcriptional Hh responsiveness of a battery of Gli-null iMEFs. Moving forward, these cell lines should prove a valuable tool set to study the unique functional regulation of the Gli proteins in a Hh-responsive cell-type.
Inhibition of cell growth and invasion by epidermal growth factor-targeted phagemid particles carrying siRNA against focal adhesion kinase in the presence of hydroxycamptothecin
Authors: Cai Xiu-Mei , Xie Hai-Long , Liu Ming-Zhu , Zha Xi-Liang 
Published: September 2008

Abstract

Background
Previous studies demonstrated the EGF-targeted phagemid particles carrying siRNA against Akt could be expressed efficiently in the presence of hydroxycamptothecin (HCPT). However, no significant cell growth inhibition was obtained. This study was to further investigate whether the EGF-targeted phagemid particles carrying siRNA would be a promising tool for anti-cancer siRNA delivery.

Results
We found that pSi4.1-siFAK phagemid particles could significantly inhibit the expression of focal adhesion kinase in the HCPT-treated cells. Moreover, we also observed that the particles could potently suppress cell growth and cell invasion.

Conclusion
These results indicated that EGF-targeted phagemid particles might be a promising tool for anti-cancer siRNA delivery in the presence of HCPT.
Recessive genetic mode of an ADH4 variant in substance dependence in African-Americans: A model of utility of the HWD test
Authors: Luo Xingguang , Zuo Lingjun , Kranzler Henry R , Wang Shuang , Anton Raymond F , Gelernter Joel 
Published: September 2008

AbstractBackgroundIn our previous studies, we reported positive associations between sevenADH4polymorphisms and substance dependence [i.e., alcohol dependence (AD) and/or drug dependence (DD)] in European-Americans (EAs). In the present study, we address the relationship betweenADH4variation and substance dependence in an African-American (AA) population, and report evidence that supports an association between a differentADH4polymorphism (rs2226896) and these phenotypes in AAs.MethodsTwo family-based association study methods, i.e., TDT and FBAT, were applied to test the relationship betweenADH4variation and substance dependence in Sample 3 (112 small nuclear families) and in Sample 4 (632 pedigrees), respectively. A population-based case-control association study method was also applied to test this relationship in 1303 unrelated subjects, with and without controlling for admixture effects. Finally, a Hardy-Weinberg Disequilibrium (HWD) test was applied to examine the association in the case-only sample, infer the genetic disease models, and distinguish the disease and non-disease factors contributing to HWD.ResultsThe marker examined was found to be in significant HWD in AA alcoholics (p = 0.0071) and drug dependent subjects (p = 0.0341), but in Hardy-Weinberg Equilibrium (HWE) in all other subgroups. Other association methods failed to detect any association between this variation and phenotypes. The best-fit genetic disease model for this marker is a recessive genetic model.ConclusionADH4variation might play a role in risk for substance dependence in AAs, potentially via a recessive mechanism. Under certain conditions, the HWD test could be a more powerful association method than conventional family-based and population-based case-control association analyses, for which, the present study provides an extreme example.
Intensive care for the adult population in Ireland: a multicentre study of intensive care population demographics
Authors:   The Irish Critical Care Trials Group
Published: September 2008

Abstract
Introduction
This prospective observational study was conducted to describe the nature of the intensive care population across Ireland, identify adherence to international benchmarks of practice, and describe patient outcomes in critically ill patients.

Methods
A prospective observational multicentre study of demographics and organ failure incidence was carried out over a 10-week period in 2006 across the intensive care units (ICUs) of 14 hospitals in both the Republic and Northern Ireland.

Results
In total, there were 1,029 patient episodes entered across 14 ICUs. Emergency admissions accounted for 70% of episodes. Admissions after major elective surgery accounted for 20.5% of admissions. The mean length of ICU stay was 5.7 days, with a median of 2 days. Severe sepsis was identified in 35% of patients during their ICU admission. Mechanical ventilation was used in 70.7% of all patients admitted, of whom 26.9% had acute lung injury. Acute kidney injury occurred in 28% of all patients. Interhospital transfers were undertaken in 85 (8.3%) patients. The overall intensive care mortality of the study population was 19%.

Conclusions
Intensive care medicine in Ireland serves a patient population with high requirement for mechanical ventilation and support of the function of multiple organs. The overall mortality compares favourably with international benchmarks.
Effects of targeted deletion of cannabinoid receptors CB1 and CB2 on immune competence and sensitivity to immune modulation by Δ9-tetrahydrocannabinol
Authors: Springs Alison E B , Karmaus Peer W F , Crawford Robert B , Kaplan Barbara L F , Kaminski Norbert E 
Published: September 2008

AbstractThe role of cannabinoid receptors, CB1 and CB2, in immune competence and modulation by Δ9-tetrahydrocannabinol (Δ9-THC) was investigated in CB1−/−/CB2−/− mice. Immunofluorescence analysis of splenic leukocytes showed no significant differences in the percentage of T cell subsets, B cells, or macrophages between wild-type and CB1−/−/CB2−/− mice. Lymphoproliferative control responses to PHA, phorbol ester plus ionomycin, or LPS and sensitivity to suppression by Δ9-THC showed no profound differences between the two genotypes, although some differences were observed in control baseline responses. Likewise, similar control responses and sensitivity to Δ9-THC were observed in mixed lymphocyte responses (MLR) and in IL-2 and IFN-γ production in both genotypes. Conversely, humoral immune responses showed a markedly different profile of activity. Δ9-THC suppressed the in vivo T cell-dependent, anti-sheep RBC (anti-sRBC) IgM antibody-forming cell (AFC) response in wild-type but not in CB1−/−/CB2−/− mice, and the in vitro anti-sRBC IgM response in CB1−/−/CB2−/− splenocytes was too low to rigorously assess CB1/CB2 involvement in modulation by Δ9-THC. Conversely, comparable in vitro IgM AFC control responses to LPS and CD40 ligand (CD40L) activation were observed in the two genotypes. Interestingly, LPS-induced IgM responses were refractory to suppression by Δ9-THC, regardless of genotype, and CD40L-induced IgM responses were only suppressed by Δ9-THC in wild-type but not in CB1−/−/CB2−/− B cells. Collectively, we demonstrate differential involvement of CB1 and/or CB2 in immune modulation by Δ9-THC and in some control responses. Moreover, CB1/CB2 involvement was observed in humoral responses requiring CD40-initiated signaling for suppression by Δ9-THC.
Induction of iNOS byChlamydophila pneumoniaerequires MyD88-dependent activation of JNK
Authors: Rodriguez Nuria , Lang Roland , Wantia Nina , Cirl Christine , Ertl Tanja , Dürr Susanne , Wagner Hermann , Miethke Thomas 
Published: September 2008

AbstractInnate immune cells produce NO via inducible NO synthase (iNOS) in response to certain infections or upon stimulation with cytokines such as IFN-γ and TNF. NO plays an important role in host defense against intracellular bacteria including Chlamydophila pneumoniae as a result of its microbicidal activity. In MyD88-deficient mice, which succumb to C. pneumoniae infection, iNOS induction is impaired 6 days postinfection, although pulmonary levels of IFN-γ and TNF are elevated as in wild-type mice at this time-point. Here, we demonstrate that induction of iNOS in macrophages upon C. pneumoniae infection is controlled by MyD88 via two pathways: NF-κB activation and phosphorylation of the MAPK JNK, which leads to the nuclear translocation of c-Jun, one of the two components of the AP-1 complex. In addition, phosphorylation of STAT1 and expression of IFN regulatory factor 1 (IRF-1) were delayed in the absence of MyD88 after C. pneumoniae infection but not after IFN-γ stimulation. Taken together, our data show that for optimal induction of iNOS during C. pneumoniae infection, the concerted action of the MyD88-dependent transcription factors NF-κB and AP-1 and of the MyD88-independent transcription factors phosphorylated STAT1 and IRF-1 is required.
MIP-3α and MIP-1α rapidly mobilize dendritic cell precursors into the peripheral blood
Authors: He Shan , Cao Qi , Yoneyama Hiroyuki , Ge Hailiang , Zhang Yi , Zhang Yanyun 
Published: September 2008

AbstractAcquisition of dendritic cells (DCs) or DC precursors in vitro is critical for DC-based immunotherapy. We reported previously that administration of MIP-1α mobilized a population of F4/80−B220−CD11c+ DC precursors into peripheral blood by the expression of CCR1 and CCR5. In this study, we identified a new subset of CCR6+CCR1−CCR5−B220−CD11c+ cells in MIP-1α-administered mice. When cultured with GM-CSF, IL-4, and TNF-α, these cells differentiated into mature DCs, possessing the typical morphologic characteristics, phenotypes, and antigen-presenting function (termed CCR6+ DC precursors). Although it did not directly drive the CCR6+ DC precursors, MIP-1α could recruit a population of F4/80+CD11c− monocyte/macrophage-producing MIP-3α in the peripheral blood to mobilize a CCR6+ DC precursor subset of B220−CD11c+ DC precursors. Importantly, exogenous administration of MIP-3α significantly enhanced MIP-1α-induced mobilization of DC precursors. Moreover, these MIP-3α- and MIP-1α-mobilized DC precursors could be prepared for a DC vaccine capable of eliciting CTL responses to tumor cells, leading to tumor rejection in vitro and in vivo. Taken together, this study further demonstrates the mechanism of DC precursor mobilization induced by MIP-1α; that is, besides mobilizing DC precursors with CCR1 and CCR5 expressions, MIP-1α recruited F4/80+CD11c− monocyte/macrophage-producing MIP-3α, which finally mobilized the CCR6+ DC precursor subset to amplify the B220−CD11c+ DC precursor population. Furthermore, combined administration of MIP-3α and MIP-1α may be an efficient strategy for collecting a large number of DCs appropriate for immunotherapy.
Skeletal Health After Continuation, Withdrawal, or Delay of Alendronate in Men With Prostate Cancer Undergoing Androgen-Deprivation Therapy
Authors: Greenspan Susan L. , Nelson Joel B. , Trump Donald L. , Wagner Julie M. , Miller Megan E. , Perera Subashan , Resnick Neil M. 
Published: September 2008

Purpose Androgen-deprivation therapy (ADT) for prostate cancer is associated with bone loss and osteoporotic fractures. Our objective was to examine changes in bone density and turnover with sustained, discontinued, or delayed oral bisphosphonate therapy in men receiving ADT. Patients and Methods A total of 112 men with nonmetastatic prostate cancer receiving ADT were randomly assigned to alendronate 70 mg once weekly or placebo in a double-blind, partial-crossover trial with a second random assignment at year 2 for those who initially received active therapy. Outcomes included bone mineral density and bone turnover markers. Results Men initially randomly assigned to alendronate and randomly reassigned at year 2 to continue had additional bone density gains at the spine (mean, 2.3% ± 0.7) and hip (mean, 1.3% ± 0.5%; both P < .01); those randomly assigned to placebo in year 2 maintained density at the spine and hip but lost (mean, −1.9% ± 0.6%; P < .01) at the forearm. Patients randomly assigned to begin alendronate in year 2 experienced improvements in bone mass at the spine and hip, but experienced less of an increase compared with those who initiated alendronate at baseline. Men receiving alendronate for 2 years experienced a mean 6.7% (± 1.2%) increase at the spine and a 3.2% (± 1.5%) at the hip (both P < .05). Bone turnover remained suppressed. Conclusion Among men with nonmetastatic prostate cancer receiving ADT, once-weekly alendronate improves bone density and decreases turnover. A second year of alendronate provides additional skeletal benefit, whereas discontinuation results in bone loss and increased bone turnover. Delay in bisphosphonate therapy appears detrimental to bone health.
Prospective Relationships of Physical Activity With Quality of Life Among Colorectal Cancer Survivors
Authors: Lynch Brigid M. , Cerin Ester , Owen Neville , Hawkes Anna L. , Aitken Joanne F. 
Published: September 2008

Purpose Physical activity can enhance quality of life for cancer survivors. However, few longitudinal studies have examined whether physical activity has a sustained effect on improvements in quality of life. The present study aims to examine the relationships between physical activity and quality of life over 2 years after a colorectal cancer diagnosis. Patients and Methods Data were collected within the Colorectal Cancer and Quality of Life Study, in which 1,966 people diagnosed with colorectal cancer were recruited through the Queensland Cancer Registry. Participants completed telephone interviews at approximately 6, 12, and 24 months after diagnosis. Generalized linear mixed models were used to estimate the overall, interindividual, and intraindividual level independent effects of participation in physical activity on quality of life. Results There was an overall independent association between physical activity and quality of life. At a given time point, participants achieving at least 150 minutes of physical activity per week had an 18% higher quality of life score than those who reported no physical activity. Significant associations were also present at the interindividual level (differences between participants) and intraindividual level (within participant changes). Conclusion These findings suggest that the positive association between physical activity and quality of life is consistent over time. Encouraging colorectal cancer survivors to be physically active may be a helpful strategy for enhancing quality of life.