bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Role of Dipeptidyl Peptidase 9 in Epidermal Growth Factor Signaling
Authors: Yao Tsun-Wen , Kim Woo-Shin , Yu Denise MT. , Sharbeen George , McCaughan Geoffrey W. , Choi Kang-Yell , Xia Pu , Gorrell Mark D. 
Published: May 2011

Abstract
Dipeptidyl peptidase IV (DPP4), DPP8, DPP9, and fibroblast activation protein (FAP), the four proteases of the DPP4 gene family, have unique peptidase and extra-enzymatic activities that have been implicated in various diseases including cancers. We report here a novel role of DPP9 in regulating cell survival and proliferation through modulating molecular signaling cascades. Akt (protein kinase B) activation was significantly inhibited by human DPP9 overexpression in human hepatoma cells (HepG2 and Huh7) and human embryonic kidney cells (HEK293T), whereas extracellular signal-regulated kinases (ERK1/2) activity was unaffected, revealing a pathway-specific effect. Interestingly, the inhibitory effect of DPP9 on Akt pathway activation was growth factor dependent. DPP9 overexpression caused apoptosis and significantly less epidermal growth factor (EGF)-mediated Akt activation in HepG2 cells. However, such inhibitory effect was not observed in cells stimulated with other growth factors, including connective tissue growth factor, hepatic growth factor, insulin or platelet-derived growth factor-BB. The effect of DPP9 on Akt did not occur when DPP9 enzyme activity was ablated by either mutagenesis or inhibition. The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is a major downstream effector of Ras. We found that DPP9 and DPP8, but not DPP4 or FAP, associate with H-Ras, a key signal molecule of the EGF receptor signaling pathway. These findings suggest an important signaling role of DPP9 in the regulation of survival and proliferation pathways. Mol Cancer Res; 9(7); 948–59. ©2011 AACR.
Aldosterone Regulates Vascular Gene Transcription via Oxidative Stress–Dependent and –Independent Pathways
Authors: Newfell Brenna G. , Iyer Lakshmanan K. , Mohammad Najwa N. , McGraw Adam P. , Ehsan Afshin , Rosano Giuseppe , Huang Paul L. , Mendelsohn Michael E. , Jaffe Iris Z. 
Published: May 2011

Objective—
Aldosterone (Aldo) antagonism prevents cardiovascular mortality by unclear mechanisms. Aldo binds to the mineralocorticoid receptor (MR), a ligand-activated transcription factor, which is expressed in human vascular cells. Here we define the early Aldo-regulated vascular transcriptome and investigate the mechanisms of gene regulation by Aldo in the vasculature that may contribute to vascular disease.

Methods and Results—
Gene expression profiling of Aldo-treated mouse aortas identified 72 genes regulated by Aldo. These genes are overrepresented in Gene Ontology categories involved in vascular function and disease. Quantitative reverse transcription–polymerase chain reaction was used to confirm and further explore mechanisms of vascular gene regulation by Aldo. Aldo-regulated vascular gene expression was inhibited by actinomycin D and MR antagonists supporting a transcriptional MR-dependent mechanism. Aldo regulation of a subset of genes was enhanced in the setting of vascular endothelial denudation and blocked by the free radical scavenger Tempol, supporting synergy between Aldo and vascular injury that is oxidative stress dependent. In the aortic arch, a region predisposed to atherosclerosis, the injury-enhanced genes also demonstrated enhanced expression compared with the descending aorta, both at baseline and after Aldo exposure. Furthermore, the clinically beneficial MR antagonist spironolactone inhibited expression of the identified genes in aortic tissue from humans with atherosclerosis.

Conclusion—
This study defines the Aldo-regulated vascular transcriptome and characterizes a subset of proatherogenic genes with enhanced Aldo-stimulated, oxidative stress–dependent expression in the setting of vascular injury and in areas predisposed to atherosclerosis. Inhibition of MR regulation of these genes may play a role in the protective effects of Aldo antagonists in patients with vascular disease, and these pathways may provide novel drug targets to prevent atherosclerosis in humans.
Hypertension Impairs Vascular Reactivity in the Pediatric Brain
Authors: Wong Linda J. , Kupferman Juan C. , Prohovnik Isak , Kirkham Fenella J. , Goodman Sharon , Paterno Kara , Sharma Madhu , Brosgol Yuri , Pavlakis Steven G. 
Published: May 2011

Background and Purpose—
Chronic hypertension impairs cerebrovascular regulation in adults, but its effects on the pediatric population are unknown. The objective of this study was to investigate cerebrovascular abnormalities in hypertensive children and adolescents.

Methods—

Sixty-four children and adolescents aged 7 to 20 years underwent transcranial Doppler examinations of the middle cerebral artery at the time of rebreathing CO
2
. Time-averaged maximum mean cerebral blood flow velocity and end-tidal CO
2
were used to quantify cerebrovascular reactivity during hypercapnia. Patients were clinically categorized as hypertensive, prehypertensive, or white coat hypertensive based on 24-hour ambulatory blood pressure measurements. Their reactivities were compared with 9 normotensive control subjects and evaluated against baseline mean blood pressure z-scores and loads.

Results—

Untreated hypertensive children had significantly lower hypercapnic reactivity than normotensive children (2.556±1.832 cm/s · mm Hg versus 4.256±1.334 cm/s · mm Hg,
P
<0.05). Baseline mean diastolic blood pressure z-scores (
r
=−0.331,
P
=0.037) and diastolic blood pressure loads (
r
=−0.351,
P
=0.026) were inversely related to reactivity.

Conclusions—
Untreated hypertensive children and adolescents have blunted reactivity to hypercapnia, indicating deranged vasodilatory reactivity. The inverse relationship between diastolic blood pressure indices and reactivity suggests that diastolic blood pressure may be a better predictor of cerebral end organ damage than systolic blood pressure.
TWO ACES
Authors: Olivot Jean-Marc , Wolford Connie , Castle James , Mlynash Michael , Schwartz Neil E. , Lansberg Maarten G. , Kemp Stephanie , Albers Gregory W. 
Published: May 2011

Background and Purpose—
To evaluate a novel emergency department-based TIA triage system.

Methods—

We developed an approach to TIA triage and management based on risk assessment using the ABCD
2
score in combination with early cervical and intracranial vessel imaging. It was anticipated that this triage system would avoid hospitalization for the majority of TIA patients and result in a low rate of recurrent stroke. We hypothesized that the subsequent stroke rate among consecutively encountered patients managed with this approach would be lower than predicted based on their ABCD
2
scores.

Results—

From June 2007 to December 2009, 224 consecutive patients evaluated in the Stanford emergency department for a possible TIA were enrolled in the study. One hundred fifty-seven were discharged to complete their evaluation at the outpatient TIA clinic; 67 patients were hospitalized. One hundred sixteen patients had a final diagnosis of TIA/minor stroke or possible TIA. The stroke rates at 7, 30, and 90 days were 0.6% (0.1%–3.5%) for patients referred to the TIA clinic and 1.5% (0.3%–8.0%) for the hospitalized patients. Combining both groups, the overall stroke rate was 0.9% (0.3%–3.2%), which is significantly less than expected based on ABCD
2
scores (
P
=0.034 at 7 days and
P
=0.001 at 90 days).

Conclusions—
This emergency department-based inpatient versus outpatient TIA triage system led to a low rate of hospitalization (30%). Recurrent stroke rates were low for both the hospitalized and outpatient subgroups.
Impairment of Cerebral Blood Flow Regulation in Astronauts With Orthostatic Intolerance After Flight
Authors: Blaber Andrew P. , Goswami Nandu , Bondar Roberta L. , Kassam Mahmood S. 
Published: May 2011

Background and Purpose—
We investigated cerebral blood flow regulation in astronauts before and after flights. We hypothesized that autoregulation would be different before flight and after flight between nonfinishers and the finishers of a stand test.

Methods—

Twenty-seven astronauts from shuttle missions lasting 8 to 16 days underwent a 10-minute stand test: 10 days before flight, 1 to 2 hours and 3 days after landing. Mean blood flow velocity of the middle cerebral artery (MCA) was measured using transcranial Doppler; Mean arterial pressure was measured using a Finapres (Ohmeda, Englewood, CO) and was adjusted to the level of the MCA (BP
MCA
). Cross-spectral power, gain, phase, and coherence were determined for the relation between BP
MCA
and the cerebrovascular resistance index mean blood flow velocity/BP
MCA
.

Results—

BP
MCA
was reduced with stand (
P
<0.001). Differences between finishers and nonfinishers (
P
=0.011) and over test days (
P
=0.004) were observed. Cerebrovascular conductance was affected by stand (
P
<0.001), by group (
P
<0.001) with a group by stand, and test day interaction (
P
<0.01). Preflight data suggest that the nonfinishers were operating at a higher cerebral vasodilation than finishers for a given BP
MCA
, and on landing day the nonfinishers had a greater decrease in mean blood flow velocity as a function of BP
MCA
with standing compared to finishers and preflight. There was a significant interaction effect of gender over the test days and from supine to stand (
P
=0.035).

Conclusions—
Our results indicate that the cause of presyncope in astronauts may be related to a mismatch of cerebral blood flow with blood pressure. Astronaut gender may also play a role in susceptibility to orthostatic intolerance after flight.
Dismal prognostic value of monosomal karyotype in elderly patients with acute myeloid leukemia: a GOELAMS study of 186 patients with unfavorable cytogenetic abnormalities
Authors: Perrot Aurore , Luquet Isabelle , Pigneux Arnaud , Mugneret Francine , Delaunay Jacques , Harousseau Jean-Luc , Barin Carole , Cahn Jean-Yves , Guardiola Philippe , Himberlin Chantal , Recher Christian , Vey Norbert , Lioure Bruno , Ojeda-Uribe Mario , Fegueux Nathalie , Berthou Christian , Randriamalala Edouard , Béné Marie C. , Ifrah Norbert , Witz Francis ,   for the GOELAMS (Groupe Ouest-Est des Leucémies Aiguës et Maladies du Sang)
Published: May 2011

AbstractThe prognosis of acute myeloid leukemia (AML) is very poor in elderly patients, especially in those classically defined as having unfavorable cytogenetics. The recent monosomal karyotype (MK) entity, defined as 2 or more autosomal monosomies or combination of 1 monosomy with structural abnormalities, has been reported to be associated with a worse outcome than the traditional complex karyotype (CK). In this retrospective study of 186 AML patients older than 60 years, the prognostic influence of MK was used to further stratify elderly patients with unfavorable cytogenetics. CK was observed in 129 patients (69%), and 110 exhibited abnormalities according to the definition of MK (59%). MK+ patients had a complete response rate significantly lower than MK− patients: 37% vs 64% (P = .0008), and their 2-year overall survival was also decreased at 7% vs 22% (P < .0001). In multivariate analysis, MK appeared as the major independent prognostic factor related to complete remission achievement (odds ratio = 2.3; 95% confidence interval, 1-5.4, P = .05) and survival (hazard ratio = 1.7; 95% confidence interval, 1.1-2.5, P = .008). In the subgroup of 129 CK+ patients, survival was dramatically decreased for MK+ patients (8% vs 28% at P = .03). These results demonstrate that MK is a major independent factor of very poor prognosis in elderly AML.
The European Sleep Apnoea Database (ESADA): report from 22 European sleep laboratories
Authors: Hedner J. , Grote L. , Bonsignore M. , McNicholas W. , Lavie P. , Parati G. , Sliwinski P. , Barbé F. , De Backer W. , Escourrou P. , Fietze I. , Kvamme J.A. , Lombardi C. , Marrone O. , Masa J.F. , Montserrat J.M. , Penzel T. , Pretl M. , Riha R. , Rodenstein D. , Saaresranta T. , Schulz R. , Tkacova R. , Varoneckas G. , Vitols A. , Vrints H. , Zielinski J. 
Published: May 2011

The European Sleep Apnoea Database (ESADA) reflects a network of 22 sleep disorder centres in Europe enabled by a COST action B26 programme. This ongoing project aims to describe differences in standard clinical care of patients with obstructive sleep apnoea (OSA) and to establish a resource for genetic research in this disorder.Patients with suspected OSA are consecutively included and followed up according to local clinical standards. Anthropometrics, medical history, medication, daytime symptoms and sleep data (polysomnography or cardiorespiratory polygraphy) are recorded in a structured web-based report form.5,103 patients (1,426 females, mean±sdage 51.8±12.6 yrs, 79.4% with apnoea/hypopnoea index (AHI) ≥5 events·h−1) were included from March 15, 2007 to August 1, 2009. Morbid obesity (body mass index ≥35 kg·m−2) was present in 21.1% of males and 28.6% of females. Cardiovascular, metabolic and pulmonary comorbidities were frequent (49.1%, 32.9% and 14.2%, respectively). Patients investigated with a polygraphic method had a lower AHI than those undergoing polysomnography (23.2±23.5versus29.1±26.3 events·h−1, p<0.0001).The ESADA is a rapidly growing multicentre patient cohort that enables unique outcome research opportunities and genotyping. The first cross-sectional analysis reveals a high prevalence of cardiovascular and metabolic morbidity in patients investigated for OSA.
Validation and comparison of several published prognostic systems for patients with small cell lung cancer
Authors: Paesmans M. , Lafitte J.J. , Lecomte J. , Berghmans T. , Efremidis A. , Giner V. , Van Cutsem O. , Scherpereel A. , Meert A.P. , Leclercq N. , Van Houtte P. , Sculier J.P. 
Published: May 2011

The aim of the present study was to validate and compare published prognostic classifications for predicting the survival of patients with small cell lung cancer.We pooled data from phase III randomised clinical trials, and used Cox models for validation purposes and concordance probability estimates for assessing predictive ability.We included 693 patients. All the classifications impacted significantly on survival, with hazard ratios (HRs) in the range 1.57–1.68 (all p<0.0001). Median survival times were 16–19 months for the best predicted groups, while they were 6–7 months for the most poorly predicted groups. Most of the paired comparisons were statistically significant. We obtained similar results when restricting the analysis to patients with extensive disease. Multivariate Cox models for fitting survival data were also performed. The HRs for a single covariate were 8.23 (95% CI 5.88–11.69), and 9.46 (6.67–13.50), and for extensive disease were 5.60 (3.13–9.93), 12.49 (5.57–28.01) and 8.83 (4.66–16.64). Concordance probability estimates ranged 0.55–0.65 (overlapping confidence intervals).Published classifications were validated and suitable for use at a population level. As expected, prediction at an individual level remains problematic. A specific model designed for extensive-disease patients did not appear to perform better.
TheTERT-CLPTM1Llocus for lung cancer predisposes to bronchial obstruction and emphysema
Authors: Wauters E. , Smeets D. , Coolen J. , Verschakelen J. , De Leyn P. , Decramer M. , Vansteenkiste J. , Janssens W. , Lambrechts D. 
Published: May 2011

Clinical studies suggest that bronchial obstruction and emphysema increase susceptibility to lung cancer. We assessed the possibility of a common genetic origin and investigated whether the lung cancer susceptibility locus on chromosome 5p15.33 increases the risk for bronchial obstruction and emphysema.Three variants in the 5p15.33 locus encompassing theTERTandCLPTM1Lgenes were genotyped in 777 heavy smokers and 212 lung cancer patients. Participants underwent pulmonary function tests and computed tomography of the chest, and completed questionnaires assessing smoking behaviour.The rs31489 C-allele correlated with reduced forced expiratory volume in 1 s (p=0.006). Homozygous carriers of the rs31489 C-allele exhibited increased susceptibility to bronchial obstruction (OR 1.82, 95% CI 1.24–2.69; p=0.002). A similar association was observed for diffusing capacity of the lung for carbon monoxide (p=0.004). Consistent with this, CC-carriers had an increased risk of emphysema (OR 2.04, 95% CI 1.41–2.94; p=1.73×10−4) and displayed greater alveolar destruction. Finally, CC-carriers also had an increased risk for lung cancer (OR 1.90, 95% CI 1.21–2.99; p=0.005), and were more susceptible to developing both lung cancer and bronchial obstruction than lung cancer alone (OR 2.11, 95% CI 1.04–4.26; p=0.038).The rs31489 variant on 5p15.33 is associated with bronchial obstruction, presence and severity of emphysema, and lung cancer.
Do responses to exercise training in cystic fibrosis depend on initial fitness level?
Authors: Gruber W. , Orenstein D.M. , Braumann K.M. 
Published: May 2011

The aim of our study was to evaluate the responses to an exercise programme with respect to initial fitness in subjects with cystic fibrosis (CF).72 subjects (42 female) aged 10–43 yrs (forced expiratory volume in 1 s of 62.0±26.7% predicted) were included. Participants were divided into three groups based on peak oxygen uptake expressed as % predicted. Subjects participated in a multifaceted rehabilitation programme, including five-times-a-week exercise training, for 6 weeks. Exercise and ventilatory capacity were determined by a maximal incremental cycling test. Oxygen uptake, workload and peak cardiac frequency at peak and submaximal workload were used as parameters for exercise capacity and responsiveness to training.Lung function values were significantly different between groups (p<0.05), and increased after training (p<0.05) only in groups with a lower initial fitness level. Responsiveness to training showed differences between groups (p<0.05) at peak and ventilatory anaerobic threshold (VAT; p<0.05), with higher improvements in subjects with lower initial fitness level.The improvements in exercise parameters in CF at peak and VAT depended on the fitness level at baseline, independent of lung function. These improvements seen after training were comparable with those seen in healthy subjects, suggesting that responsiveness to exercise is similar in CF and in healthy untrained persons.
Exacerbation of cigarette smoke-induced pulmonary inflammation by Staphylococcus aureus Enterotoxin B in mice
Authors: Huvenne Wouter , Lanckacker Ellen A , Krysko Olga , Bracke Ken R , Demoor Tine , Hellings Peter W , Brusselle Guy G , Joos Guy F , Bachert Claus , Maes Tania 
Published: May 2011

Abstract

Background
Cigarette smoke (CS) is a major risk factor for the development of COPD. CS exposure is associated with an increased risk of bacterial colonization and respiratory tract infection, because of suppressed antibacterial activities of the immune system and delayed clearance of microbial agents from the lungs. Colonization with Staphylococcus aureus results in release of virulent enterotoxins, with superantigen activity which causes T cell activation.

Objective
To study the effect of Staphylococcus aureus enterotoxin B (SEB) on CS-induced inflammation, in a mouse model of COPD.

Methods
C57/Bl6 mice were exposed to CS or air for 4 weeks (5 cigarettes/exposure, 4x/day, 5 days/week). Endonasal SEB (10 μg/ml) or saline was concomitantly applied starting from week 3, on alternate days. 24 h after the last CS and SEB exposure, mice were sacrificed and bronchoalveolar lavage (BAL) fluid and lung tissue were collected.

Results
Combined exposure to CS and SEB resulted in a raised number of lymphocytes and neutrophils in BAL, as well as increased numbers of CD8+ T lymphocytes and granulocytes in lung tissue, compared to sole CS or SEB exposure. Moreover, concomitant CS/SEB exposure induced both IL-13 mRNA expression in lungs and goblet cell hyperplasia in the airway wall. In addition, combined CS/SEB exposure stimulated the formation of dense, organized aggregates of B- and T- lymphocytes in lungs, as well as significant higher CXCL-13 (protein, mRNA) and CCL19 (mRNA) levels in lungs.

Conclusions
Combined CS and SEB exposure aggravates CS-induced inflammation in mice, suggesting that Staphylococcus aureus could influence the pathogenesis of COPD.
Gender differences and determinants of health related quality of life in coronary patients: a follow-up study
Authors: Dueñas María , Ramirez Carmen , Arana Roque , Failde Inmaculada 
Published: May 2011

Abstract

Background
The role of gender differences in Health Related Quality Life (HRQL) in coronary patients is controversial, so understanding the specific determinants of HRQL in men and women might be of clinical importance. The aim of this study was to know the gender differences in the evolution of HRQL at 3 and 6 months after a coronary event, and to identify the key clinical, demographic and psychological characteristics of each gender associated with these changes.

Methods
A follow-up study was carried out, and 175 patients (112 men and 63 women) with acute myocardial infarction (AMI) or unstable angina were studied. The SF-36v1 health questionnaire was used to assess HRQL, and the GHQ-28 (General Health Questionnaire) to measure mental health during follow-up. To study the variables related to changes in HRQL, generalized estimating equation (GEE) models were performed.

Results
Follow-up data were available for 55 men and 25 women at 3 months, and for 35 men and 12 women at 6 months. Observations included: a) Revascularization was performed later in women. b) The frequency of rehospitalization between months 3 and 6 of follow-up was higher in women c) Women had lower baseline scores in the SF-36. d) Men had progressed favourably in most of the physical dimensions of the SF-36 at 6 months, while at the same time women's scores had only improved for Physical Component Summary, Role Physical and Social Functioning; e) the variables determining the decrease in HRQL in men were: worse mental health and angina frequency; and in women: worse mental health, history of the disease, revascularization, and angina frequency.

Conclusions
There are differences in the evolution of HRQL, between men and women after a coronary attack. Mental health is the determinant most frequently associated with HRQL in both genders. However, other clinical determinants of HRQL differed with gender, emphasizing the importance of individualizing the intervention and the content of rehabilitation programs. Likewise, the recognition and treatment of mental disorders in these patients could be crucial.