bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endovascular treatment of paraclinoid aneurysms: 142 aneurysms in one centre
Authors: Wang Yang , Li Youxiang , Jiang Chuhan , Jiang Fan , Meng Hui , Siddiqui Adnan H , Yang Xinjian 
Published: October 2012

BackgroundCurrent endovascular techniques have been widely used to treat paraclinoid aneurysms.MethodsFrom January 2009 to December 2011, 126 consecutive patients with 142 saccular paraclinoid aneurysms were treated with endovascular embolization at our institute. A retrospective review of the clinical and imaging data was performed.ResultsOf the 142 aneurysms, 121 (86.2%) had small while 21 (14.8%) had large fundus size. 83 aneurysms (58.5%) were narrow necked and 59 (41.5%) were wide necked. The dome–neck ratio was favorable in 26 aneurysms (18.3%) and unfavorable in 116 (81.7%). 24 aneurysms (16.9%) were managed with coil embolization and 118 (83.1%) with a stent assisted coiling technique. Immediate angiography demonstrated complete occlusion in 62 (43.7%), neck remnant occlusion in 47 (33.1%), and residual aneurysm occlusion in 33 (23.2%) aneurysms. The overall recurrence rate in the 112 aneurysms with angiographic follow-up (8.88±3.40 months, mean±SD) was 12.5%. Of the 14 recurrent aneurysms, 10 were managed with endovascular treatment (six by stent assisted coiling, four by coiling) while four are under observation. There were six (4.3%) procedural complications during 137 procedures. Clinical follow-up was available for 119 patients (94%) with a follow-up time of 16.6±13.6 months, and the majority (98%) had a modified Rankin scale score of 0–1.ConclusionsThe stent assisted coiling technique is effective for the treatment of paraclinoid aneurysms. Small paraclinoid aneurysms (≤10 mm) are suitable for endovascular treatment, with a low rate of recurrence. In contrast, large paraclinoid aneurysms (>10 mm) treated with current endovascular techniques exhibited a high rate of recurrence.
Modulation of the ATPase and Transport Activities of Broad-Acting Multidrug Resistance Factor ABCC10 (MRP7)
Authors: Malofeeva Ekaterina V. , Domanitskaya Natalya , Gudima Mariya , Hopper-Borge Elizabeth A. 
Published: October 2012

Abstract
The cell surface molecule ABCC10 is a broad-acting transporter of xenobiotics, including cancer drugs, such as taxanes, epothilone B, and modulators of the estrogen pathway. Abcc10−/− mice exhibit increased tissue sensitivity and lethality resulting from paclitaxel exposure compared with wild-type counterparts, arguing ABCC10 functions as a major determinant of taxane sensitivity in mice. To better understand the mechanistic basis of ABCC10 action, we characterized the biochemical and vectorial transport properties of this protein. Using crude membranes in an ABCC10 overexpression system, we found that the ABCC10 transport substrates estrogen estradiol-glucuronide (E217βG) and leukotriene C4 (LTC4) significantly stimulated ABCC10 beryllium fluoride (BeFx)-sensitive ATPase activity. We also defined the E217βG antagonist, tamoxifen, as a novel substrate and stimulator of ABCC10. In addition, a number of cytotoxic substrates, including docetaxel, paclitaxel, and Ara-C, increased the ABCC10 basal ATPase activity. We determined that ABCC10 localizes to the basolateral cell surface, using transepithelial well assays to establish that ABCC10-overexpressing LLC-PK1 cells exported [3H]-docetaxel from the apical to the basolateral side. Importantly, we found that the clinically valuable multikinase inhibitor sorafenib, and a natural alkaloid, cepharanthine, inhibited ABCC10 docetaxel transport activity. Thus, concomitant use of these agents might restore the intracellular accumulation and potency of ABCC10-exported cytotoxic drugs, such as paclitaxel. Overall, our work could seed future efforts to identify inhibitors and other physiologic substrates of ABCC10. Cancer Res; 72(24); 6457–67. ©2012 AACR.
Benign Breast Disease and the Risk of Subsequent Breast Cancer in African American Women
Authors: Cote Michele L. , Ruterbusch Julie J. , Alosh Barra , Bandyopadhyay Sudeshna , Kim Elizabeth , Albashiti Bassam , Sharaf Aldeen Bashar , Radisky Derek C. , Frost Marlene H. , Visscher Daniel W. , Hartmann Lynn C. , Nassar Warzecha Hind , Ali-Femhi Rouba 
Published: October 2012

Abstract
Benign breast disease (BBD) is an established risk factor for breast cancer among Caucasian women but less is known about BBD in African American women. As African American women suffer from disproportionate mortality due to breast cancer, special focus on pathologic characteristics that may influence disease risk is warranted.
Benign breast biopsies from African American women were identified by the University Pathology Group (Detroit, MI). African American women of ages 20 to 84 years, who underwent a breast biopsy from 1997 to 2000, were eligible for the study. Subsequent breast cancers were identified through a linkage with the Detroit Surveillance Epidemiology and End Results (SEER) program. The first biopsy was reviewed by the pathologist, and lesions were classified following Dupont and Page criteria along with involution and other histologic features. Logistic regression was used to estimate the risk of developing a subsequent breast cancer with the histologic characteristics of BBD.
A total of 1,406 BBD biopsies from African American women were included in this study with a median follow-up of 10.1 years. The majority (68%) showed nonproliferative disease, 29% had proliferative disease without atypia, and 3% had proliferative disease with atypia. Subsequent incident breast cancers occurred in 55 women (3.9%). Women whose biopsies showed proliferative disease with atypia were more than three-fold more likely to develop breast cancer as compared with women who had nonproliferative disease [relative risk (RR) 3.29, 95% confidence interval (CI) 1.21–8.93].
Better characterization of the risk of breast cancer among women with BBD, considering both ethnicity and detailed molecular findings, can lead to better surveillance, earlier diagnosis, and potentially improved survival. Cancer Prev Res; 5(12); 1375–80. ©2012 AACR.
Inhibition of Notch1 Signaling Reduces Abdominal Aortic Aneurysm in Mice by Attenuating Macrophage-Mediated Inflammation
Authors: Hans Chetan P. , Koenig Sara N. , Huang Nianyuan , Cheng Jeeyun , Beceiro Susana , Guggilam Anuradha , Kuivaniemi Helena , Partida-Sánchez Santiago , Garg Vidu 
Published: October 2012

Objective—
Activation of inflammatory pathways plays a critical role in the development of abdominal aortic aneurysms (AAA). Notch1 signaling is a significant regulator of the inflammatory response; however, its role in AAA is unknown.

Methods and Results—

In an angiotensin II–induced mouse model of AAA, activation of Notch1 signaling was observed in the aortic aneurysmal tissue of
Apoe
−/−
mice, and a similar activation of Notch1 was observed in aneurysms of humans undergoing AAA repair.
Notch1
haploinsufficiency significantly reduced the incidence of AAA in
Apoe
−/−
mice in response to angiotensin II. Reconstitution of bone marrow–derived cells from
Notch1
+/−
;Apoe
−/−
mice (donor) in lethally irradiated
Apoe
−/−
mice (recipient) decreased the occurrence of aneurysm. Flow cytometry and immunohistochemistry demonstrated that
Notch1
haploinsufficiency prevented the influx of inflammatory macrophages at the aneurysmal site by causing defects in macrophage migration and proliferation. In addition, there was an overall reduction in the inflammatory burden in the aorta of the
Notch1
+/−
;Apoe
−/−
mice compared with the
Apoe
−/−
mice. Last, pharmacological inhibition of Notch1 signaling also prevented AAA formation and progression in
Apoe
−/−
mice.

Conclusion—
Our data suggest that decreased levels of Notch1 protect against the formation of AAA by preventing macrophage recruitment and attenuating the inflammatory response in the aorta.
Retinol-Binding Protein 4 Is an Independent Factor Associated With Triglycerides and a Determinant of Very Low-Density Lipoprotein–Apolipoprotein B100 Catabolism in Type 2 Diabetes Mellitus
Authors: Vergès Bruno , Guiu Boris , Cercueil Jean Pierre , Duvillard Laurence , Robin Isabelle , Buffier Perrine , Bouillet Benjamin , Aho Serge , Brindisi Marie Claude , Petit Jean Michel 
Published: October 2012

Objective—
Retinol-binding protein 4 (rbp4) is an adipokine secreted by adipocytes and liver, whose levels are elevated in type 2 diabetes mellitus (T2DM). Plasma levels of rbp4 and triglycerides are strongly correlated in T2DM. However, we do not know whether this association is direct or indirect via liver fat content, and the link between rbp4 and triglyceride metabolism remains unknown.

Methods and Results—

Liver fat measurement by proton spectroscopy was performed in 221 patients with T2DM, and an in vivo kinetic study with stable isotopes was carried out in 14 patients with T2DM. In multivariate analysis, triglycerides were associated positively with rbp4 (β=0.273,
P
<0.0001), apolipoprotein (apo) B (β=0.258,
P
<0.0001), and liver fat (β=0.191,
P
=0.002) and negatively with high-density lipoprotein cholesterol (β=−0.442,
P
<0.0001). rbp4 was correlated positively with apoB100 very-low-density lipoprotein (VLDL) pool (
r
=0.62,
P
=0.017) and negatively with VLDL-apoB100 total fractional catabolic rate (
r
=−0.66,
P
=0.001). In multivariate analysis, rbp4 (
P
=0.015), plasma triglycerides (
P
=0.024), and sex (
P
=0.026) were independently associated with VLDL-apoB100 total fractional catabolic rate.

Conclusion—
In T2DM, plasma rbp4 level is associated with plasma triglycerides, independently of liver fat content. There is a strong independent negative correlation between plasma rbp4 and VLDL-apoB100 total fractional catabolic rate. These data suggest that rbp4 may be involved in the pathophysiology of hypertriglyceridemia in T2DM by reducing VLDL catabolism.
Mitochondrial Calcium and Reactive Oxygen Species Regulate Agonist-Initiated Platelet Phosphatidylserine Exposure
Authors: Choo Hyo-Jung , Saafir Talib B. , Mkumba Laura , Wagner Mary B. , Jobe Shawn M. 
Published: October 2012

Objective—
To study the interactions of cytoplasmic calcium elevation, mitochondrial permeability transition pore (mPTP) formation, and reactive oxygen species formation in the regulation of phosphatidylserine (PS) exposure in platelets.

Methods and Results—

mPTP formation, but not the degree of cytoplasmic calcium elevation, was associated with PS exposure in wild-type, cyclophilin D–null, ionomycin-treated, and reactive oxygen species–treated platelets. In the absence of the mPTP regulator cyclophilin D, agonist-initiated mPTP formation and high-level PS exposure were markedly blunted, but cytoplasmic calcium transients were unchanged. Mitochondrial calcium (Ca
2+
mit
) transients and reactive oxygen species, key regulators of mPTP formation, were examined in strongly stimulated platelets. Increased reactive oxygen species production occurred in strongly stimulated platelets and was dependent on extracellular calcium entry, but not the presence of cyclophilin D. Ca
2+
mit
increased significantly in strongly stimulated platelets. Abrogation of Ca
2+
mit
entry, either by inhibition of the Ca
2+
mit
uniporter or mitochondrial depolarization, prevented mPTP formation and exposure but not platelet aggregation or granule release.

Conclusion—

Sustained cytoplasmic calcium levels are necessary, but not sufficient, for high-level PS exposure in response to agonists. Increased Ca
2+
mit
levels are a key signal initiating mPTP formation and PS exposure. Blockade of Ca
2+
mit
entry allows the specific inhibition of platelet procoagulant activity.
Induction of Anti-Anti-Idiotype Antibodies Against Sulfated Glycosaminoglycans Reduces Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Brito Víctor , Mellal Katia , Portelance Simon Giroux , Pérez Arlenis , Soto Yosdel , deBlois Denis , Ong Huy , Marleau Sylvie , Vázquez Ana María 
Published: October 2012

Objective—
The pathogenesis of atherosclerosis is associated with the early retention of low-density lipoproteins that are trapped in the extracellular matrix of the arterial intima by interaction with glycosaminoglycan side chains of proteoglycans. Mutant mouse/human chimeric antibodies of the murine monoclonal antibody P3, which react with N-glycolyl–containing gangliosides and sulfated glycosaminoglycans, were tested for their potentially antiatherogenic properties through the induction of an idiotypic antibody network that may specifically interfere with the binding of low-density lipoproteins to proteoglycan side chains, low-density lipoprotein modification, and foam cell formation.

Methods and Results—

Apolipoprotein E–deficient mice fed a high-fat, high-cholesterol diet received 5 to 6 doses of chP3R99 or chP3S98 mutant antibodies, showing high and low reactivity, respectively, against their respective antigens. Both chimeric antibodies elicited an immunodominant anti-idiotypic response in the absence of adjuvant. A striking (40%–43%) reduction (
P
<0.01) in total lesion areas was observed in 18-week-old mice immunized with chP3R99, but not chP3S98, compared with PBS-treated mice. The antiatherosclerotic effect was associated with increased mice sera reactivity against heparin and sulfated glycosaminoglycans, including chondroitin and dermatan sulfate. In addition, purified IgG from chP3R99-immunized mice blocked the retention of apolipoprotein B–containing lipoproteins within the arterial wall of apolipoprotein E
−/−
mice.

Conclusion—
The present study supports use of active immunization and the mounting of an idiotypic antibody network response against glycosaminoglycans as a novel approach to target atherosclerosis.
Interference of the CD30–CD30L Pathway Reduces Atherosclerosis Development
Authors: Foks Amanda C. , Bot Ilze , Frodermann Vanessa , de Jager Saskia C.A. , ter Borg Mariette , van Santbrink Peter J. , Yagita Hideo , Kuiper Johan , van Puijvelde Gijs H.M. 
Published: October 2012

Objective—
Costimulatory molecules tightly control immune responses by providing positive signals that promote T-cell activation or by transducing inhibitory signals that limit T-cell responses. CD30 and CD30L are members of the tumor necrosis factor receptor superfamily and are involved in the activation and proliferation of T and B cells, which have been implicated in the initiation and progression of atherosclerosis. In the present study, we thus aimed to determine the role of the CD30–CD30L pathway in the development of atherosclerosis.

Methods and Results—

Western-type diet–fed low-density lipoprotein receptor–deficient mice were treated with an anti-CD30L antibody for 8 weeks, which resulted in a reduction of atherosclerotic lesion formation in the aortic root by 35%. Reduced numbers of adventitial CD3
+
T cells were found in anti-CD30L–treated mice, whereas no differences were observed in collagen and macrophage content of the atherosclerotic lesions. B-cell and mast cell responses were also not affected on anti-CD30L treatment. Interestingly, splenocyte proliferation was reduced by 53%, whereas T-cell numbers were concomitantly reduced in anti-CD30L–treated mice compared with control mice. These data thus indicate that the CD30–CD30L pathway solely exerts its function via inhibition of T-cell responses.

Conclusion—
In the present study, we are the first to show that interruption of the CD30–CD30L pathway reduced initial atherosclerosis development by modulating T-cell function.
Hypertension Susceptibility Loci and Blood Pressure Response to Antihypertensives
Authors: Gong Yan , McDonough Caitrin W. , Wang Zhiying , Hou Wei , Cooper-DeHoff Rhonda M. , Langaee Taimour Y. , Beitelshees Amber L. , Chapman Arlene B. , Gums John G. , Bailey Kent R. , Boerwinkle Eric , Turner Stephen T. , Johnson Julie A. 
Published: October 2012

Background—
To date, 39 single nucleotide polymorphisms (SNPs) have been associated with blood pressure (BP) or hypertension in genome-wide association studies in whites. Our hypothesis is that the loci/SNPs associated with BP/hypertension are also associated with BP response to antihypertensive drugs.

Methods and Results—

We assessed the association of these loci with BP response to atenolol or hydrochlorothiazide monotherapy in 768 hypertensive participants in the Pharmacogenomics Responses of Antihypertensive Responses study. Linear regression analysis was performed on whites for each SNP in an additive model adjusting for baseline BP, age, sex, and principal components for ancestry. Genetic scores were constructed to include SNPs with nominal associations, and empirical
P
values were determined by permutation test. Genotypes of 37 loci were obtained from Illumina 50K cardiovascular or Omni1M genome-wide association study chips. In whites, no SNPs reached Bonferroni-corrected α of 0.0014, 6 reached nominal significance (
P
<0.05), and 3 were associated with atenolol BP response at
P
<0.01. The genetic score of the atenolol BP-lowering alleles was associated with response to atenolol (
P
=3.3×10
–6
for systolic BP;
P
=1.6×10
–6
for diastolic BP). The genetic score of the hydrochlorothiazide BP-lowering alleles was associated with response to hydrochlorothiazide (
P
=0.0006 for systolic BP;
P
=0.0003 for diastolic BP). Both risk score
P
values were <0.01 based on the empirical distribution from the permutation test.

Conclusions—
These findings suggest that selected signals from hypertension genome-wide association studies may predict BP response to atenolol and hydrochlorothiazide when assessed through risk scoring.

Clinical Trial Registration Information—

clinicaltrials.gov
; Identifier: NCT00246519.
Immunoglobulins Against Tyrosine-Nitrated Epitopes in Coronary Artery Disease
Authors: Thomson Leonor , Tenopoulou Margarita , Lightfoot Richard , Tsika Epida , Parastatidis Ioannis , Martinez Marissa , Greco Todd M. , Doulias Paschalis-Thomas , Wu Yuping , Tang W.H. Wilson , Hazen Stanley L. , Ischiropoulos Harry 
Published: October 2012

Background—
Several lines of evidence support a pathophysiological role of immunity in atherosclerosis. Tyrosine-nitrated proteins, a footprint of oxygen- and nitrogen-derived oxidants generated by cells of the immune system, are enriched in atheromatous lesions and in circulation of patients with coronary artery disease (CAD). However, the consequences of possible immune reactions triggered by the presence of nitrated proteins in subjects with clinically documented atherosclerosis have not been explored.

Methods and Results—
Specific immunoglobulins that recognize 3-nitrotyrosine epitopes were identified in human lesions, as well as in circulation of patients with CAD. The levels of circulating immunoglobulins against 3-nitrotyrosine epitopes were quantified in patients with CAD (n=374) and subjects without CAD (non-CAD controls, n=313). A 10-fold increase in the mean level of circulating immunoglobulins against protein-bound 3-nitrotyrosine was documented in patients with CAD (3.75±1.8 μg antibody Eq/mL plasma versus 0.36±0.8 μg antibody Eq/mL plasma), and was strongly associated with angiographic evidence of significant CAD.

Conclusions—
The results of this cross-sectional study suggest that posttranslational modification of proteins via nitration within atherosclerotic plaque-laden arteries and in circulation serve as neo-epitopes for the elaboration of immunoglobulins, thereby providing an association between oxidant production and the activation of the immune system in CAD.
Cerebrovascular Reserve and Stroke Risk in Patients With Carotid Stenosis or Occlusion
Authors: Gupta Ajay , Chazen J. Levi , Hartman Maya , Delgado Diana , Anumula Nikesh , Shao Huibo , Mazumdar Madhu , Segal Alan Z. , Kamel Hooman , Leifer Dana , Sanelli Pina C. 
Published: October 2012

Background and Purpose—
Impairments in cerebrovascular reserve (CVR) have been variably associated with increased risk of ischemic events and may stratify stroke risk in patients with high-grade internal carotid artery stenosis or occlusion. The purpose of this study is to perform a systematic review and meta-analysis to summarize the association of CVR impairment and stroke risk.

Methods—
We performed a literature search evaluating the association of impairments in CVR with future stroke or transient ischemic attack in patients with high-grade internal carotid artery stenosis or occlusion. We included studies with a minimum of 1-year patient follow-up with baseline CVR measures performed by any modality and primary outcome measures of stroke and/or transient ischemic attack. A meta-analysis with assessment of study heterogeneity and publication bias was performed. Results were presented in a forest plot and summarized using a random-effects model.

Results—
Thirteen studies met the inclusion criteria, representing a total of 1061 independent CVR tests in 991 unique patients with a mean follow-up of 32.7 months. We found a significant positive relationship between impairment of CVR and development of stroke with a pooled random effects OR of 3.86 (95% CI, 1.99–7.48). Subset analysis showed that this association between CVR impairment and future risk of stroke/transient ischemic attack remained significant regardless of ischemic outcome measure, symptomatic or asymptomatic disease, stenosis or occlusion, or CVR testing method.

Conclusions—
CVR impairment is strongly associated with increased risk of ischemic events in carotid stenosis or occlusion and may be useful for stroke risk stratification.
The dynamics of word retrieval in major depression
Authors: Douglas Katie M , Porter Richard J , Knight Robert G , Alsop Brent 
Published: October 2012

Objective: Impairment in the retrieval of specific episodes from autobiographical memory is commonly observed in major depression. However, it is unclear whether impairment in retrieval processes is a general characteristic of major depression or is confined to the recollection of personal memories. This study examined the time course of the retrieval of words from semantic memory. Method: A letter fluency test was administered to 65 inpatients with major depression and 50 healthy controls. A two-parameter model was fit to the decay curve representing the production of words over a 90-second period. One parameter, N, is an estimate of the total number of words that would be generated if the respondent was given unlimited time. The other, tau, is the average of the difference in time between the first word generated and each subsequent word. Results: There was evidence of a deficit in the retrieval of words from long-term memory in depressed patients. The significant difference between groups suggested that even if given an extended period of time in which to respond to compensate for possible slowness, the depressed group would not retrieve as many words as the controls. The retrieval failure could not be attributed solely to cognitive slowing or the effects of antidepressant medication. Conclusions: The results extend findings of a deficit in the process of retrieving specific episodes from autobiographical memory and suggest that a generalised impairment in memory retrieval may be characteristic of major depression.