bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short sleep duration is associated with enhanced endothelin-1 vasoconstrictor toneThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.
Authors: Weil Brian R. , Mestek Michael L. , Westby Christian M. , Van Guilder Gary P. , Greiner Jared J. , Stauffer Brian L. , DeSouza Christopher A. 
Published: August 2010

Short sleep duration is associated with increased cardiovascular disease (CVD) morbidity. Endothelial vasomotor dysfunction represents a potential mechanism contributing to the increased CVD risk associated with habitual short sleep duration. Endothelin (ET)-1 is a potent vasoconstrictor peptide that is associated with endothelial vasomotor dysfunction and increased CVD risk. Currently, there is no information regarding the influence of short sleep duration on ET-1 vasoconstrictor activity in adults. We tested the hypothesis that ET-1-mediated vasoconstrictor activity is greater in adults who sleep less than 7 h/night (short sleep duration) compared with those who sleep 7–9 h/night (normal sleep duration). Forearm blood flow (FBF) responses to intra-arterial infusion of BQ-123 (100 nmol/min for 60 min), a selective ETAreceptor antagonist, were determined in 80 adults: 50 with normal sleep duration (32 males and 18 females; age: 56.6 ± 1.2 years; sleep: 7.6 ± 0.1 h/night) and 30 with short sleep duration (17 males and 13 females; age: 56.5 ± 1.2 years; sleep: 6.1 ± 0.1 h/night). In response to BQ-123, adults reporting short sleep duration had a greater increase in resting FBF compared with adults reporting normal sleep duration (~20% vs. ~8%; P < 0.05). There was an inverse relation between mean nightly sleep duration and the FBF response to BQ-123 at 60 min (r = –0.29, P < 0.05). These findings indicate that habitual short sleep duration is associated with greater ET-1-mediated vasoconstrictor tone. Increased ET-1 vasoconstrictor activity may contribute to the elevated CVD risk associated with chronic reductions in sleep duration.
ETA receptors are present in human aortic vascular endothelial cells and modulate intracellular calciumThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.
Authors: Avedanian Levon , Riopel Julie , Bkaily Ghassan , Nader Moni , D’Orleans-Juste Pedro , Jacques Danielle 
Published: August 2010

Using immunofluorescence and real 3-D confocal microscopy, our results showed the presence of ET-1, ETA, and ETB receptors in isolated human aortic vascular endothelial cells (hVECs). The level of the peptide and its receptors was significantly higher in the nucleus (including the nuclear envelope membranes) than in the cytosol (including the cell membrane). Furthermore, using the Western blot technique we demonstrated the presence of both ETA and ETB receptors. Using intact and isolated human hVECs and the Fura-2 calcium (Ca2+) measurement technique, we showed that ET-1 induced a dose-dependent increase of total intracellular free Ca2+, with an EC50 of 1.3 × 10−10 mol/L. The specific ETA receptor antagonist ABT-627 (10−7 mol/L), but not the ETB receptor antagonist A-192621 (10−7 mol/L), prevented the ET-1 (10−9 mol/L) induced increase of total intracellular Ca2+. In conclusion, these results clearly show that similar to ETB receptors, ETA receptors are also present in human aortic vascular endothelial cells and their levels are higher than ETB in the nucleus when compared with the cytosol. Furthermore, we suggest that ETA, but not ETB, receptors mediate the effect of ET-1 on total intracellular Ca2+ of human aortic vascular endothelial cells.
TAK-701, a Humanized Monoclonal Antibody to Hepatocyte Growth Factor, Reverses Gefitinib Resistance Induced by Tumor-Derived HGF in Non–Small Cell Lung Cancer with an EGFR Mutation
Authors: Okamoto Wataru , Okamoto Isamu , Tanaka Kaoru , Hatashita Erina , Yamada Yuki , Kuwata Kiyoko , Yamaguchi Haruka , Arao Tokuzo , Nishio Kazuto , Fukuoka Masahiro , Jänne Pasi A. , Nakagawa Kazuhiko 
Published: August 2010

Abstract
Most non–small cell lung cancer (NSCLC) tumors with an activating mutation of the epidermal growth factor receptor (EGFR) are initially responsive to EGFR tyrosine kinase inhibitors (TKI) such as gefitinib but ultimately develop resistance to these drugs. Hepatocyte growth factor (HGF) induces EGFR-TKI resistance in NSCLC cells with such a mutation. We investigated strategies to overcome gefitinib resistance induced by HGF. Human NSCLC cells with an activating EGFR mutation (HCC827 cells) were engineered to stably express HGF (HCC827-HGF cells). HCC827-HGF cells secreted large amounts of HGF and exhibited resistance to gefitinib in vitro to an extent similar to that of HCC827 GR cells, in which the gene for the HGF receptor MET is amplified. A MET-TKI reversed gefitinib resistance in HCC827-HGF cells as well as in HCC827 GR cells, suggesting that MET activation induces gefitinib resistance in both cell lines. TAK-701, a humanized monoclonal antibody to HGF, in combination with gefitinib inhibited the phosphorylation of MET, EGFR, extracellular signal-regulated kinase, and AKT in HCC827-HGF cells, resulting in suppression of cell growth and indicating that autocrine HGF-MET signaling contributes to gefitinib resistance in these cells. Combination therapy with TAK-701 and gefitinib also markedly inhibited the growth of HCC827-HGF tumors in vivo. The addition of TAK-701 to gefitinib is a promising strategy to overcome EGFR-TKI resistance induced by HGF in NSCLC with an activating EGFR mutation. Mol Cancer Ther; 9(10); 2785–92. ©2010 AACR.
Resveratrol Modulates Drug- and Carcinogen-Metabolizing Enzymes in a Healthy Volunteer Study
Authors: Chow H-H. Sherry , Garland Linda L. , Hsu Chiu-Hsieh , Vining Donna R. , Chew Wade M. , Miller Jessica A. , Perloff Marjorie , Crowell James A. , Alberts David S. 
Published: August 2010

Abstract
Resveratrol has been shown to exhibit cancer-preventive activities in preclinical studies. We conducted a clinical study to determine the effect of pharmacologic doses of resveratrol on drug- and carcinogen-metabolizing enzymes. Forty-two healthy volunteers underwent baseline assessment of cytochrome P450 (CYP) and phase II detoxification enzymes. CYP1A2, CYP2D6, CYP2C9, and CYP3A4 enzyme activities were measured by the metabolism of caffeine, dextromethorphan, losartan, and buspirone, respectively. Blood lymphocyte glutathione S-transferase (GST) activity and GST-π level and serum total and direct bilirubin, a surrogate for UDP-glucuronosyl transferase (UGT) 1A1 activity, were measured to assess phase II enzymes. After the baseline evaluation, study participants took 1 g of resveratrol once daily for 4 weeks. Enzyme assessment was repeated upon intervention completion. Resveratrol intervention was found to inhibit the phenotypic indices of CYP3A4, CYP2D6, and CYP2C9 and to induce the phenotypic index of 1A2. Overall, GST and UGT1A1 activities were minimally affected by the intervention, although an induction of GST-π level and UGT1A1 activity was observed in individuals with low baseline enzyme level/activity. We conclude that resveratrol can modulate enzyme systems involved in carcinogen activation and detoxification, which may be one mechanism by which resveratrol inhibits carcinogenesis. However, pharmacologic doses of resveratrol could potentially lead to increased adverse drug reactions or altered drug efficacy due to inhibition or induction of certain CYPs. Further clinical development of resveratrol for cancer prevention should consider evaluation of lower doses of resveratrol to minimize adverse metabolic drug interactions. Cancer Prev Res; 3(9); 1168–75. ©2010 AACR.
A Dominant-Negative c-jun Mutant Inhibits Lung Carcinogenesis in Mice
Authors: Tichelaar Jay W. , Yan Ying , Tan Qing , Wang Yian , Estensen Richard D. , Young Matthew R. , Colburn Nancy H. , Yin Hulian , Goodin Colleen , Anderson Marshall W. , You Ming 
Published: August 2010

Abstract
Lung cancer is the leading cause of cancer mortality in the United States and worldwide. The identification of key regulatory and molecular mechanisms involved in lung tumorigenesis is therefore critical to increase our understanding of this disease and could ultimately lead to targeted therapies to improve prevention and treatment. Induction of members of the activator protein-1 (AP-1) transcription factor family has been described in human non–small cell lung carcinoma. Activation of AP-1 can either stimulate or repress transcription of multiple gene targets, ultimately leading to increased cell proliferation and inhibition of apoptosis. In the present study, we show induction of AP-1 in carcinogen-induced mouse lung tumors compared with surrounding normal lung tissue. We then used a transgenic mouse model directing conditional expression of the dominant-negative c-jun mutant TAM67 in lung epithelial cells to determine the effect of AP-1 inhibition on mouse lung tumorigenesis. Consistent with low AP-1 activity in normal lung tissue, TAM67 expression had no observed effects in adult mouse lung. TAM67 decreased tumor number and overall lung tumor burden in chemically induced mouse lung tumor models. The most significant inhibitory effect was observed on carcinoma burden compared with lower-grade lesions. Our results support the concept that AP-1 is a key regulator of mouse lung tumorigenesis, and identify AP-1–dependent transcription as a potential target to prevent lung tumor progression. Cancer Prev Res; 3(9); 1148–56. ©2010 AACR.
Enhanced Induction of Mucin-Depleted Foci in Estrogen Receptor β Knockout Mice
Authors: Saleiro Diana , Murillo Genoveva , Lubahn Dennis B. , Kopelovich Levy , Korach Kenneth S. , Mehta Rajendra G. 
Published: August 2010

Abstract
The role of the estrogen receptor β (ERβ) in the colon has received considerable interest, yet in vivo models are needed to better define its protective actions. In the present study, wild-type (WT), ERα, and ERβ knockout (αERKO and βERKO) mice were injected with azoxymethane, a colon chemical carcinogen. Fourteen weeks after azoxymethane exposure, the incidence of aberrant crypt foci (ACF) was assessed by methylene blue staining. βERKO mice showed significantly higher incidence (P &lt; 0.001) of ACF (15.0 ± 2.5) compared with αERKO (3.4 ± 1.0) and WT (4.6 ± 1.0) mice. The colons in several βERKO mice had increased thickness and loss of normal morphology. It has been reported that ERβ plays a role in the maintenance of the colonic crypt architecture; this may explain the loss of crypt organization in the colonic epithelium of βERKO mice. The presence of mucin-depleted foci (MDF) has been shown, both in humans and in rodents, as an early event in colon cancer. Therefore, to surpass the limitations with ACF scoring, we performed Alcian blue-neutral red staining to assess the presence of MDF. This assay allowed the assessment of precancerous lesions on all the βERKO mice colons (38.3 ± 4.0; P &lt; 0.001), comparing to WT and αERKO mice (6.6 ± 1.5 and 10.0 ± 1.9, respectively), and served to confirm the ACF results. Together, these data support the use of MDF staining as a biomarker for precancerous lesions and the protective role of ERβ in colon carcinogenesis. Cancer Prev Res; 3(9); 1198–204. ©2010 AACR.
Optimal Medical Therapy for Non–ST-Segment–Elevation Acute Coronary Syndromes
Authors: Bagnall Alan J. , Yan Andrew T. , Yan Raymond T. , Lee Cindy H. , Tan Mary , Baer Carolyn , Polasek Petr , Fitchett David H. , Langer Anatoly , Goodman Shaun G. ,   for the Canadian Acute Coronary Syndromes Registry II Investigators
Published: August 2010

Background—
Acute coronary syndrome (ACS) patients in the highest risk categories are least likely to receive evidence-based treatments (EBTs). We sought to determine why physicians do not prescribe EBTs for patients with non–ST-segment–elevation ACSs and the factors determining use of these treatments after 1 year.

Methods and Results—
One thousand nine hundred fifty-six non–ST-segment-elevation ACS patients were enrolled in the prospective, multicenter Canadian ACS registry II between October 2002 and December 2003. Each patient's physician gave reasons why guideline-indicated medication(s) was not prescribed during hospitalization. Medication use and reason(s) for discontinuation after 1 year were obtained by telephone interview of the patients. The commonest reason for not prescribing EBTs was “not high-enough risk” or “no evidence/guidelines to support use.” However, Global Registry of Acute Coronary Events scores of patients not treated for this reason were often similar to or higher than those of patients prescribed such treatment. After 1 year, 77% of patients not on optimal ACS treatment at discharge remained without optimal treatment, and overall antiplatelet, β-blocker, and angiotensin-converting enzyme inhibitor use declined. Approximately one third of patients not taking EBTs had stopped their medication without instruction from their doctor.

Conclusions—
Nonprovision of EBTs may be due to subjective underestimation of patient risk and hence, likely treatment benefit. Oversights in care delivery were also apparent. Objective risk stratification, combined with efforts to ensure provision and adherence to EBTs, should be encouraged.
Prediction of 1-Year Mortality With Different Measures of ST-Segment Recovery in All-Comers After Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction
Authors: Verouden Niels J.W. , Haeck Joost D.E. , Kuijt Wichert J. , van Geloven Nan , Koch Karel T. , Henriques José P.S. , Baan Jan , Vis Marije M. , Piek Jan J. , Tijssen Jan G.P. , de Winter Robbert J. 
Published: August 2010

Background—
Post hoc analyses from several randomized, controlled trials have established the prognostic importance of different measures of ST-segment recovery in highly selected patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment–elevation myocardial infarction (STEMI). In this single-center registry, we investigated whether various measures of ST-segment recovery can be applied to unselected STEMI patients undergoing primary PCI.

Methods and Results—

We analyzed 12-lead ECGs from 2124 consecutive STEMI patients who underwent primary PCI at our institution between November 1, 2000, and January 1, 2007. ECGs were recorded at the catheterization laboratory immediately before arterial puncture and at the end of PCI. We examined measures assessing ST-segment recovery on the postprocedural ECG and measures comparing both ECGs and related these to 1-year, all-cause mortality. Cumulative ST-segment recovery (∑ST-D resolution) at a 50% cutoff had the highest unadjusted accuracy (C statistic, 0.646; 95% confidence interval, 0.602 to 0.689;
P
<0.001) as compared with the other 8 measures evaluated. Furthermore, ∑ST-D resolution was the strongest contributor to both the net reclassification and integrated discrimination improvement.

Conclusions—
Although each measure of ST-segment recovery provided univariable prognostic information, the ∑ST-D resolution measure comparing summed ST-segment deviations on the preprocedural and postprocedural ECG was the best independent predictor of 1-year mortality in all-comer STEMI patients after primary PCI.
Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors Versus β-Blockers as Second-Line Therapy for Hypertension
Authors: Magid David J. , Shetterly Susan M. , Margolis Karen L. , Tavel Heather M. , O'Connor Patrick J. , Selby Joe V. , Ho P. Michael 
Published: August 2010

Background—
Trials comparing hypertension monotherapies have found either no difference or modest differences in blood pressure (BP) and cardiovascular events. However, no trial has assessed the comparative effectiveness of 2nd-line therapy in patients whose BP was not controlled with a thiazide diuretic.

Methods and Results—

This was an observational study conducted with a hypertension registry of adults enrolled in 3 large integrated health care delivery systems from 2002 to 2007. Patients newly started on thiazide monotherapy whose BP remained uncontrolled were observed after addition of either an angiotensin-converting enzyme (ACE) inhibitor or β-blocker for subsequent BP control and cardiovascular events. Patients for whom either add-on drug was indicated or contraindicated were excluded. After adjustment for patient characteristics and study year, BP control during the subsequent 6 to 18 months was comparable for the 2 agents (70.5% ACE, 69.0% β-blockers;
P
=0.09). Rates of incident myocardial infarction (hazard ratio, 1.05; 95% confidence interval, 0.69 to 1.58) and stroke (hazard ratio, 1.01; 95% confidence interval, 0.68 to 1.52) were also similar for the ACE inhibitor and β-blocker groups during an average of 2.3 years of follow-up. There were also no differences in heart failure or renal function.

Conclusions—
ACE inhibitors and β-blockers are equally effective in lowering BP and preventing cardiovascular events for patients whose BP is not controlled with a thiazide diuretic alone and who have no compelling indication for a specific 2nd-line agent.
All-Inside Meniscal Repair with Bioabsorbable Meniscal Screws or with Bioabsorbable Meniscus Arrows
Authors: Järvelä Sally , Sihvonen Raine , Sirkeoja Hannu , Järvelä Timo 
Published: August 2010

Background All-inside meniscal repairs have gained popularity in the past few years. However, only a few prospective, randomized clinical studies have been done to compare different all-inside meniscal repair techniques. Hypothesis Meniscal repair with bioabsorbable meniscal screws and arrows results in similar clinical outcome on short-term follow-up. Study Design Randomized controlled trial; Level of evidence, 2. Methods Forty-two patients were prospectively randomized to have all-inside meniscal repair either by using bioabsorbable meniscal screws or bioabsorbable meniscus arrows (21 patients, 23 meniscal repairs in each group) for the fixation. The evaluation methods were clinical examination, Lysholm score, the International Knee Documentation Committee (IKDC) knee score, and magnetic resonance arthrography (MRA) evaluation. The average follow-up time was 27 months (standard deviation, 8). Results There were no differences between the study groups preoperatively. All 42 patients (100%) were available for the follow-up. However, during the follow-up, 11 patients had clinical failure, confirmed at second-look arthroscopy, of the repair leading to partial meniscal resection. Four failures (all on the medial meniscus) were observed with the use of meniscal screw fixation (17%), and 7 (4 on the medial meniscus, and 3 on the lateral meniscus) with the use of meniscus arrow fixation (30%) (P = .242). Six patients with meniscus arrows (29%) had chondral damage on the femoral condyles evaluated by MRA or at second-look arthroscopy, while none of the patients with the meniscal screws had the same (P = .018). However, the Lysholm and the IKDC scores were similar in both groups at follow-up. Conclusion All-inside meniscal repair with bioabsorbable meniscal screws and arrows resulted in similar clinical outcome, although significantly more chondral damage was observed when using bioabsorbable meniscus arrows for fixation.
Medial Patellofemoral Ligament Repair for Recurrent Patellar Dislocation
Authors: Camp Christopher L. , Krych Aaron J. , Dahm Diane L. , Levy Bruce A. , Stuart Michael J. 
Published: August 2010

Background The medial patellofemoral ligament (MPFL) is the primary restraint to extreme lateral displacement and is typically disrupted with an acute lateral patellar dislocation. Patients who fail a comprehensive nonoperative program and experience recurrent lateral patellar instability episodes are candidates for surgical treatment. Current surgical procedures include a variety of proximal realignment techniques, including repair or reconstruction of the MPFL along with distal realignment of the tibial tubercle when indicated. Purpose The objective of this study was to review the clinical, functional, and radiographic outcomes of isolated MPFL repair for recurrent lateral patellar dislocation. Study Design Case series; Level of evidence, 4. Methods The records of all patients undergoing MPFL repair for recurrent patellar dislocation at the Mayo Clinic from 2001 to 2006 were retrospectively reviewed. Twenty-seven patients (29 knees) with an average age of 19 years (range, 11-32 years) were included in this study. Clinical, functional, and radiographic outcomes were assessed at an average of 4 years after surgery (range, 2-7 years), using recurrent instability as the primary end point. Results The success rate of MPFL repair for preventing recurrent dislocations was 72% (21 of 29 knees). Eight patients (28%) experienced a recurrent lateral patellar dislocation. Five of these patients required a reoperation, including two MPFL reconstructions, 1 tibial tubercle osteotomy with MPFL reconstruction, 1 tibial tubercle osteotomy with revision MPFL repair, and 1 revision MPFL repair. At final follow-up, the mean Lysholm and Kujala scores were 86 (range, 42-100) and 92 (range, 57-105), respectively. Postoperative radiographs revealed a mean patellofemoral congruence angle improvement of 27° (range, 5°-44°). The only statistically significant risk factor for failure was nonanatomical MPFL repair at the medial femoral condyle (P = .004). Conclusion Isolated repair of the MPFL for recurrent patellar instability is associated with a relatively high failure rate, but remains a viable surgical option if surgical technique principles are followed. The clinical success of this operation depends on restoration of the anatomical origin of the MPFL and careful patient selection.
High School Concussions in the 2008-2009 Academic Year
Authors: Meehan William P. , d'Hemecourt Pierre , Dawn Comstock R. 
Published: August 2010

Background An estimated 136 000 concussions occur per academic year in high schools alone. The effects of repetitive concussions and the potential for catastrophic injury have made concussion an injury of significant concern for young athletes. Purpose The objective of this study was to describe the mechanism of injury, symptoms, and management of sport-related concussions using the High School Reporting Information Online (HS RIO) surveillance system. Study Design Descriptive epidemiology study. Methods All concussions recorded by HS RIO during the 2008-2009 academic year were included. Analyses were performed using SPSS software. Chi-square analysis was performed for all categorical variables. Statistical significance was considered for P < .05. Results A total of 544 concussions were recorded. The most common mechanism (76.2%) was contact with another player, usually a head-to-head collision (52.7%). Headache was experienced in 93.4%; 4.6% lost consciousness. Most (83.4%) had resolution of their symptoms within 1 week. Symptoms lasted longer than 1 month in 1.5%. Computerized neuropsychological testing was used in 25.7% of concussions. When neuropsychological testing was used, athletes were less likely to return to play within 1 week than those for whom it was not used (13.6% vs 32.9%; P < .01). Athletes who had neuropsychological testing appeared less likely to return to play on the same day (0.8% vs 4.2%; P = .056). A greater proportion of injured, nonfootball athletes had computerized neuropsychological testing than injured football players (23% vs 32%; P = .02) Conclusion When computerized neuropsychological testing is used, high school athletes are less likely to be returned to play within 1 week of their injury. Concussed football players are less likely to have computerized neuropsychological testing than those participating in other sports. Loss of consciousness is relatively uncommon among high school athletes who sustain a sport-related concussion. The most common mechanism is contact with another player. Some athletes (1.5%) report symptoms lasting longer than 1 month.