bluuebunny/crossref_metadata_2025_split huggingface dataset:
2-Nitrobenzoate 2-Nitroreductase (NbaA) Switches Its Substrate Specificity from 2-Nitrobenzoic Acid to 2,4-Dinitrobenzoic Acid under Oxidizing Conditions
Authors: Kim Yong-Hak , Song Woo-Seok , Go Hayoung , Cha Chang-Jun , Lee Cheolju , Yu Myeong-Hee , Lau Peter C. K. , Lee Kangseok 
Published: November 2012

ABSTRACT

2-Nitrobenzoate 2-nitroreductase (NbaA) of
Pseudomonas fluorescens
strain KU-7 is a unique enzyme, transforming 2-nitrobenzoic acid (2-NBA) and 2,4-dinitrobenzoic acid (2,4-DNBA) to the 2-hydroxylamine compounds. Sequence comparison reveals that NbaA contains a conserved cysteine residue at position 141 and two variable regions at amino acids 65 to 74 and 193 to 216. The truncated mutant Δ65-74 exhibited markedly reduced activity toward 2,4-DNBA, but its 2-NBA reduction activity was unaffected; however, both activities were abolished in the Δ193-216 mutant, suggesting that these regions are necessary for the catalysis and specificity of NbaA. NbaA showed different lag times for the reduction of 2-NBA and 2,4-DNBA with NADPH, and the reduction of 2,4-DNBA, but not 2-NBA, failed in the presence of 1 mM dithiothreitol or under anaerobic conditions, indicating oxidative modification of the enzyme for 2,4-DNBA. The enzyme was irreversibly inhibited by 5,5′-dithio-
bis
-(2-nitrobenzoic acid) and ZnCl
2
, which bind to reactive thiol/thiolate groups, and was eventually inactivated during the formation of higher-order oligomers at high pH, high temperature, or in the presence of H
2
O
2
. SDS-PAGE and mass spectrometry revealed the formation of intermolecular disulfide bonds by involvement of the two cysteines at positions 141 and 194. Site-directed mutagenesis indicated that the cysteines at positions 39, 103, 141, and 194 played a role in changing the enzyme activity and specificity toward 2-NBA and 2,4-DNBA. This study suggests that oxidative modifications of NbaA are responsible for the differential specificity for the two substrates and further enzyme inactivation through the formation of disulfide bonds under oxidizing conditions.
Risk of contrast-induced nephropathy in patients undergoing endovascular treatment of acute ischemic stroke
Authors: Sharma Jitendra , Nanda Ashish , Jung Richard S , Mehta Sonal , Pooria Javad , Hsu Daniel P 
Published: November 2012

Background and purposeWe report the incidence and risk factors for contrast-induced nephropathy after the use of iodinated contrast for endovascular treatment of acute ischemic stroke.MethodsA retrospective chart review was performed in 194 consecutive patients who underwent endovascular treatment for acute ischemic stroke between January 2006 and January 2011. No patients were excluded from treatment for elevated creatinine (Cr). Each patient received approximately 150 ml intra-arterial non-ionic low-osmolar contrast agent (Optiray 320) during the endovascular procedure. Contrast-induced nephropathy (CIN) was defined according to the Acute Kidney Injury Network criteria as a relative increase of serum Cr 50% above the baseline or an absolute increase of 0.3 mg/dl at 48 h following the endovascular procedure.ResultsOf 194 patients (mean age 65±14 years), 52% were women (n=100) and 25% (n=48) were diabetic. Baseline Cr levels for 191 patients ranged between 0.4 and 2.7 mg/dl. Three patients on chronic hemodialysis had baseline Cr levels ranging between 5.3 and 6.1 mg/dl. Cr was ≤1.5 mg/dl in 163 patients (84%) and ≥ 1.5 mg/dl in 31 (16%). Three of the 191 patients (1.5%) developed CIN as noted from Cr measurements between baseline and within 48 h. One patient who developed an elevated Cr level had a known history of chronic renal insufficiency (Cr > 1.5 mg/dl) and two had baseline Cr levels within the normal range. An additional CT angiogram was obtained in 44 patients, none of which developed CIN. Female gender and diabetes were not associated with a higher risk of developing CIN.ConclusionsThe risk of developing CIN is low among patients with acute stroke who undergo emergency endovascular treatment. Treatment of acute stroke should be performed irrespective of Cr levels.
Transfemoral endovascular treatment of atherosclerotic stenotic lesions of the left common carotid artery ostium: case series and review of the literature
Authors: Dumont Travis M , Eller Jorge L , Mokin Maxim , Snyder Kenneth V , Hopkins L Nelson , Levy Elad I , Siddiqui Adnan H 
Published: November 2012

ObjectiveEndovascular treatment of atherosclerotic stenosis of the left common carotid artery ostium (LCCAO) represents a technical challenge. Unlike stenting of other supra-aortic trunk lesions, LCCAO stenting is not able to be performed from a retrograde approach through the brachial artery. Stenting may be performed via a retrograde approach with a carotid artery cut-down or with total endovascular technique via a transfemoral approach. A consecutive case series is presented to demonstrate the feasibility and safety of the endovascular transfemoral LCCAO stenting technique.MethodsOur prospectively maintained database of elective neuroendovascular procedures was searched for cases of LCCAO angioplasty and stenting for atherosclerotic stenosis performed between January 2003 and April 2012. Cases identified were isolated and analyzed for clinical and anatomic data. The primary outcome of interest was the incidence of periprocedural (30-day) neurological or cardiopulmonary complications.ResultsFourteen patients were treated with a transfemoral approach (mean arterial stenosis 72%; symptomatic lesions 86%). Six (43%) had tandem stenosis of the proximal left internal carotid artery. In these cases, embolic protection was used. Stent revascularization was a technical success in all 14 patients, resulting in <20% residual stenosis in each. One intraprocedural complication (transient ischemic attack) was noted in a patient with symptomatic stenosis. One additional patient was identified who was treated with retrograde stenting due to bilateral leg amputations and no femoral access, with no periprocedural complication.ConclusionsIn our experience, transfemoral stenting of stenotic LCCAO lesions is feasible and no permanent neurological or cardiopulmonary sequelae occurred in 14 patients treated with this technique.
Targeting C4-Demethylating Genes in the Cholesterol Pathway Sensitizes Cancer Cells to EGF Receptor Inhibitors via Increased EGF Receptor Degradation
Authors: Sukhanova Anna , Gorin Andrey , Serebriiskii Ilya G. , Gabitova Linara , Zheng Hui , Restifo Diana , Egleston Brian L. , Cunningham David , Bagnyukova Tetyana , Liu Hanqing , Nikonova Anna , Adams Gregory P. , Zhou Yan , Yang Dong-Hua , Mehra Ranee , Burtness Barbara , Cai Kathy Q. , Klein-Szanto Andres , Kratz Lisa E. , Kelley Richard I. , Weiner Louis M. , Herman Gail E. , Golemis Erica A. , Astsaturov Igor 
Published: November 2012

AbstractPersistent signaling by the oncogenic EGF receptor (EGFR) is a major source of cancer resistance to EGFR targeting. We established that inactivation of 2 sterol biosynthesis pathway genes, SC4MOL (sterol C4-methyl oxidase–like) and its partner, NSDHL (NADP-dependent steroid dehydrogenase–like), sensitized tumor cells to EGFR inhibitors. Bioinformatics modeling of interactions for the sterol pathway genes in eukaryotes allowed us to hypothesize and then extensively validate an unexpected role for SC4MOL and NSDHL in controlling the signaling, vesicular trafficking, and degradation of EGFR and its dimerization partners, ERBB2 and ERBB3. Metabolic block upstream of SC4MOL with ketoconazole or CYP51A1 siRNA rescued cancer cell viability and EGFR degradation. Inactivation of SC4MOL markedly sensitized A431 xenografts to cetuximab, a therapeutic anti-EGFR antibody. Analysis of Nsdhl-deficient Bpa1H/+ mice confirmed dramatic and selective loss of internalized platelet-derived growth factor receptor in fibroblasts, and reduced activation of EGFR and its effectors in regions of skin lacking NSDHL.Significance: This work identifies a critical role for SC4MOL and NSDHL in the regulation of EGFR signaling and endocytic trafficking and suggests novel strategies to increase the potency of EGFR antagonists in tumors. Cancer Discov; 3(1); 96–111. ©2012 AACR.This article is highlighted in the In This Issue feature, p. 1
Transcriptome Analysis for Notch3 Target Genes Identifies Grip2 as a Novel Regulator of Myogenic Response in the Cerebrovasculature
Authors: Fouillade Charles , Baron-Menguy Céline , Domenga-Denier Valérie , Thibault Christelle , Takamiya Kogo , Huganir Richard , Joutel Anne 
Published: November 2012

Objective—
Notch3 is critically important for the structure and myogenic response of distal arteries, particularly of cerebral arteries. However, signaling pathways acting downstream of Notch3 remain largely unknown.

Methods and Results—

Transcriptome analysis using tail arteries of Notch3-null mice identified a core set of 17 novel Notch3-regulated genes confirmed in tail or brain arteries. Postnatal deletion of RBP-Jκ in smooth muscle cells recapitulated the structural, functional, and molecular defects of brain arteries induced by Notch3 deficiency. Transient in vivo blockade of the Notch pathway with γ-secretase inhibitors uncovered, in addition to
Notch3
, 6 immediate responders, including the voltage-gated potassium channel Kv1.5, which opposes to myogenic constriction of brain arteries, and the glutamate receptor–interacting protein 2 (Grip2) with no previously established role in the cerebrovasculature. We identified a vascular smooth muscle cell isoform of
Grip2
. We showed that Notch3–RBP-Jκ specifically regulates this isoform. Finally, we found that cerebral arteries of Grip2 mutant mice, which express an N-terminally truncated Grip2 protein, exhibited selective attenuation of pressure-induced contraction.

Conclusion—
Our data provide insight into how Notch3 signals in the brain arteries, establishing the postnatal requirement of smooth muscle RBP-Jκ in this context. Notch3-regulated transcriptome provides potential for modulating myogenic response in the cerebrovasculature.
Heritability of Venous Biomechanics
Authors: Molnár Andrea Àgnes , Tárnoki Àdám Domonkos , Tárnoki Dávid László , Kulcsár Zoltán , Littvay Levente , Garami Zsolt , Préda István , Kiss Róbert Gábor , Bérczi Viktor , Lannert Àgnes , Monos Emil , Nádasy György László 
Published: November 2012

Objective—
Altered venous biomechanics may contribute to the pathogenesis of venous diseases, and their heritability is less known.

Methods and Results—
Seventy-eight monozygotic twin pairs (aged 42.4±16.8 years) and 24 same-sex dizygotic twin pairs (aged 50.5±16.1 years) were examined. Anteroposterior and mediolateral diameters of the common femoral vein were measured by ultrasonography. Measurements were made both in supine and in standing body positions, with or without controlled forced expiration (Valsalva test). High correlation of diameter, capacity, and distensibility values was found between twin pairs. The univariate heritability (A), shared (C), and unshared (E) environmental effects model has shown 39.3% genetic component of the variance of low pressure, 37.9% of high-pressure venous capacity, and 36.4% of maximal capacity changes, even after elimination of sex, age, and body weight effects. Bivariate Cholesky analysis revealed substantial covariance of inherited body weight and venous capacity components (57.0%–81.4%).

Conclusion—
Femoral vein capacity and elasticity depend ≈30% to 40% on genetic factors, and this value in the standing body position can reach 50%. A relatively high genetic covariance was found between weight and femoral vein capacity and elasticity. Our work might yield some new insights into the inheritance of venous diseases that are associated with altered venous biomechanics and help elucidate the involved genes.
Conversion of Cardiovascular Conference Abstracts to Publications
Authors: Fosbøl Emil L. , Fosbøl Philip L. , Harrington Robert A. , Eapen Zubin J. , Peterson Eric D. 
Published: November 2012

Background—
The transition of scientific knowledge from discovery into practice is less than ideal. A key step in this translation occurs when presentations from major meetings are published in peer-reviewed literature, yet the completeness and speed of this process are not known. We performed a systematic and automated evaluation of rates, timing, and correlates of publication from scientific abstracts presented at 3 major cardiovascular conferences.

Methods and Results—

Using an automated computer algorithm, we searched the ISI Web of Science to identify peer-reviewed publications of abstracts presented at the American Heart Association (AHA), American College of Cardiology (ACC), and European Society of Cardiology (ESC) scientific sessions from 2006 to 2008. We compared abstract publication rates and journal impact factor between the 3 meetings using multivariable logistic regression modeling. From 2006 to 2008, 11 365, 5005, and 10 838 abstracts were presented at the AHA, ACC, and ESC meetings, respectively. Overall, 30.6% of presented abstracts were published within 2 years of the conference; ranging from 34.5% for AHA to 29.5% for ACC to 27.0% for ESC (
P
<0.0001). Five years after conference presentation in 2005, these rates had risen slightly to 49.7% for AHA, 42.6% for ACC, and 37.6% for ESC (
P
<0.0001). After adjustment for abstract characteristics and contributing countries, abstracts presented at the AHA meeting remained more likely for publication relative to the ESC (adjusted odds ratio, 1.24; 95% confidence interval, 1.16–1.34) and the ACC (adjusted odds ratio, 1.20; 95% confidence interval, 1.11–1.29). Median impact factors for subsequent publications varied from 4.8 (interquartile range, 3.8–10.1) for AHA to 4.0 (interquartile range, 3.1–7.5) for ACC and 3.9 (quartile 1–3, 2.5–5.8) for ESC (
P
for difference between groups <0.01). Clinical science and population science were less likely to be published compared with basic science.

Conclusions—
One third of abstracts were translated into publications by 2 years after presentation and less than one half by 5 years after presentation. Our findings suggest that efforts to understand the barriers to publication and to facilitate the rapid dissemination of new knowledge are needed to speed up the transition of scientific discovery into clinical practice.
Venous Thromboembolism Risk in Ischemic Stroke Patients Receiving Extended-Duration Enoxaparin Prophylaxis: Results From the EXCLAIM Study
Authors: Turpie Alexander G.G. , Hull Russell D. , Schellong Sebastian M. , Tapson Victor F. , Monreal Manuel , Samama Meyer-Michel , Chen Min , Yusen Roger D. ,   for the EXCLAIM Investigators
Published: November 2012

Background and Purpose—
The optimal duration of venous thromboembolism prophylaxis in acute stroke patients is unknown. This subanalysis of the Extended Prophylaxis for Venous ThromboEmbolism in Acutely Ill Medical Patients With Prolonged Immobilization (EXCLAIM) study investigated extended-duration thromboprophylaxis with enoxaparin, compared with placebo following standard-duration enoxaparin, in ischemic stroke patients.

Methods—
Acutely ill medical patients with recently reduced mobility received open-label enoxaparin 40 mg for 10±4 days, and they were then randomized to double-blind enoxaparin 40 mg daily or placebo for further 28±4 days. Venous thromboembolism incidence (symptomatic/asymptomatic deep-vein thrombosis, symptomatic/fatal pulmonary embolism) up to day 28 after randomization and major bleeding rates up to 48 h after the last dose of study treatment were reported.

Results—
In total, 389 of 5963 (6.5%) randomized patients had ischemic stroke: 198 received extended-duration prophylaxis and 191 placebo. Extended-duration prophylaxis reduced venous thromboembolism incidence versus placebo (2.4% versus 8.0%; absolute risk difference, −5.6%; 95% CI, −10.5% to −0.7%), but it was associated with an increase in major bleeding (1.5% versus 0% in enoxaparin and placebo groups; absolute risk difference, +1.5%; 95% CI, −0.2% to 3.2%).

Conclusion—
Extended-duration thromboprophylaxis with enoxaparin was associated with reduced venous thromboembolism risk and increased major bleeding in the subgroup of patients with ischemic stroke in the EXCLAIM study.

Clinical Trial Registration Information—

URL:
http://clinicaltrials.gov
. Unique Identifier: NCT00077753.
Physical Activity Prevents Progression for Cognitive Impairment and Vascular Dementia
Authors: Verdelho Ana , Madureira Sofia , Ferro José M. , Baezner Hansjörg , Blahak Christian , Poggesi Anna , Hennerici Michael , Pantoni Leonardo , Fazekas Franz , Scheltens Philip , Waldemar Gunhild , Wallin Anders , Erkinjuntti Timo , Inzitari Domenico 
Published: November 2012

Background and Purpose—
We aimed to study if physical activity could interfere with progression for cognitive impairment and dementia in older people with white matter changes living independently.

Methods—
The LADIS (Leukoaraiosis and Disability) prospective multinational European study evaluates the impact of white matter changes on the transition of independent elderly subjects into disability. Subjects were evaluated yearly during 3 years with a comprehensive clinical protocol and cognitive assessment with classification of cognitive impairment and dementia according to usual clinical criteria. Physical activity was recorded during the clinical interview. MRI was performed at entry and at the end of the study.

Results—

Six hundred thirty-nine subjects were included (74.1±5 years old, 55% women, 9.6±3.8 years of schooling, 64% physically active). At the end of follow-up, 90 patients had dementia (vascular dementia, 54; Alzheimer disease with vascular component, 34; frontotemporal dementia, 2), and 147 had cognitive impairment not dementia. Using Cox regression analysis, physical activity reduced the risk of cognitive impairment (dementia and not dementia: β=−0.45,
P
=0.002; hazard ratio, 0.64; 95% CI, 0.48–0.85), dementia (β=−0.49,
P
=0.043; hazard ratio, 0.61; 95% CI, 0.38–0.98), and vascular dementia (β=−0.86,
P
=0.008; hazard ratio, 0.42; 95% CI, 0.22–0.80), independent of age, education, white matter change severity, medial temporal atrophy, previous and incident stroke, and diabetes.

Conclusions—
Physical activity reduces the risk of cognitive impairment, mainly vascular dementia, in older people living independently.
Randomized Controlled Trial of Symptomatic Middle Cerebral Artery Stenosis
Authors: Miao Zhongrong , Jiang Lidan , Wu Hao , Bao Yuhai , Jiao Liqun , Li Shenmao , Wu Jian , Hua Yang , Li Yan , Zhu Junlei , Zhu Fengshui , Liu Xuezong , Ling Feng 
Published: November 2012

Background and Purpose—
To investigate the efficacy and safety of percutaneous transluminal angioplasty and stenting (PTAS) for symptomatic middle cerebral artery stenosis compared with standard medical treatment in a low-risk Chinese population.

Methods—
A prospective, randomized, controlled, single-center clinical trial was conducted comparing PTAS with medical treatment for symptomatic middle cerebral artery stenosis (≥70%). Patients were enrolled according to 1:1 enroll ratio (PTAS: medical). The PTAS group received stenting or balloon angioplasty, whereas the medical treatment group received standard medical treatment (aspirin 100mg plus clopidogrel 75mg/d), and all the patients were under strict control of the risk factors. The end point events were any kind of ipsilateral stroke or transient ischemic attack, or death from any origin during 1-year follow-up.

Results—

The enrollment was stopped after 70 patients were enrolled from August 2007 to December 2010, with a 30-day rate of end point events of 8.3% versus 5.9% (
P
=0.69) for PTAS and medical group, respectively, and 1-year rate of end point events of 19.4% versus 17.6% (
P
=0.85), respectively. There was no significant difference in baseline characteristics between the 2 groups. The mean follow-up time, which was ongoing, was 9.9 ± 3.9 and 9.7 ± 4.4 months, respectively. Among the risk factors, hypertension was the independent related to the outcome (
P
=0.015).

Conclusions—
This study showed that endovascular treatment is as safe but not better than medical treatment for symptomatic middle cerebral artery stenosis in a low-risk Chinese population. History of hypertension increases the risk of recurrent ischemic events.
Early Insulin Glycemic Control Combined With tPA Thrombolysis Reduces Acute Brain Tissue Damages in a Focal Embolic Stroke Model of Diabetic Rats
Authors: Fan Xiang , Ning MingMing , Lo Eng H. , Wang Xiaoying 
Published: November 2012

Background and Purpose—
Therapeutic effects of early insulin glycemic control for poststroke hyperglycemia in combination with tissue-type plasminogen activator (tPA) thrombolytic therapy have not yet been studied but are of great clinical interest. In this study, we tested the effects of insulin plus tPA combination in a model of focal embolic stroke in Type I diabetic rats.

Methods—
Streptozotocin was used to produce Type I diabetes in male Wistar rats for 6 weeks and then embolic focal strokes were induced. All rats were treated with insulin or saline at 1 hour followed by tPA or saline at 1.5 hour after stroke. Mortality, infarction, hemispheric swelling, hemorrhagic transformation, and perfusion defects were examined at 24 hours after stroke. Total plasma plasminogen activator inhibitor-1 antigen and activity levels were measured before stroke and 1.5, 3, and 6 hours after stroke by ELISA.

Results—
Early insulin glycemic control alone or tPA thrombolysis alone had no significant effects on ischemic infarction. However, early insulin glycemic control combined with tPA significantly reduced brain infarction and swelling, ameliorated tPA-associated hemorrhagic transformation, and improved plasma perfusion at 24 hours after stroke. We also found that the combination significantly decreased plasma plasminogen activator inhibitor-1 antigen level at 6 hours and plasminogen activator inhibitor-1 activity at 1.5 and 6 hours after stroke.

Conclusions—
Early insulin glycemic control may be beneficial in combination with tPA thrombolysis for ischemic stroke with diabetes mellitus or poststroke hyperglycemia.
The Importance of the Number of Reflux Episodes in the Diagnosis of Laryngopharyngeal Reflux Disease
Authors: Fusconi Massimo , De Virgilio Armando , Conte Michela , Colicchio Maria Giovanna , Gallo Andrea , Greco Antonio , Ralli Giovanni , de Vincentiis Marco 
Published: November 2012

ObjectiveThe aim of this study is to evaluate the sensitivity parameters of the percentage of time the pH is <4 and >7, as well as the total number of laryngopharyngeal reflux episodes in 24 hours, in patients with suspected laryngopharyngeal reflux disease.Study DesignRetrospective controlled study.SettingUniversity hospital.Subjects and MethodsThe study was conducted on 46 patients with laryngopharyngeal reflux disease and 58 healthy controls. Patients and controls underwent 24 hours of dual‐probe pH monitoring of the distal and cervical esophagus. Patients completed a Reflux Symptom Index questionnaire and underwent esophageal manometry. Data concerning the percentage of time the pH was <4 and >7 and the number of reflux episodes registered at the cervical esophagus were collected and evaluated.ResultsThe percentage of time the pH is <4 and the number of laryngopharyngeal reflux episodes seem to be a reliable diagnostic laryngopharyngeal reflux criterion reaching satisfactory sensitivity (81% and 83%, respectively). Although the pH >7 parameter appeared statistically different between the 2 groups (P <. 001), the sensitivity of the test appeared to be poor (55%).ConclusionOur study demonstrates the importance of the absolute number of laryngopharyngeal reflux episodes in 24 hours in the diagnosis of patients with suspected laryngopharyngeal reflux, proposing it as a new diagnostic criterion.