bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Effects of Heat-Treated Silica Xerogel Induced by Incorporation of Chlorophyll Species
Authors: Martínez J. R. , Martínez-Castañón G. , Ortega-Zarzosa G. , de la Cruz-Mendoza J. A. , Palomares-Sánchez S. A. , Ruiz Facundo
Published: November 2007

Composites containing chlorophyll aggregates dispersed in amorphous silica are of interest because of their optical attractive properties. The silica powders added with chlorophyll species, prepared by the sol-gel method, were studied using X-ray diffraction, IR spectroscopy and differential temperature analysis. Silica xerogel samples were prepared using an ethanol/H2O/TEOS molar ratio of 4:11.6:1 and loaded with extracts from frozen spinach leaves. The silica xerogel microstructure of the powders was studied as a function of the annealing temperature. We found in our samples partial crystallization of the glass matrix in form of tridymite and cristobalite phases and quenching centers or nonfluorescing aggregates due to denaturation of photosystem promoted by chlorophyll decomposition after400∘C.
AnM-Estimation-Based Procedure for Determining the Number of Regression Models in Regression Clustering
Authors: Rao C. R. , Wu Y. , Shao Q.
Published: November 2007

In this paper, a procedure based onM-estimation to determine the number of regression models for the problem of regression clustering is proposed. We have shown that the true classification is attained whennincreases to infinity under certain mild conditions, for instance, without assuming normality of the distribution of the random errors in each regression model.
Soluble Triggering Receptor Expressed on Myeloid Cells 1 Is Released in Patients with Stable Chronic Obstructive Pulmonary Disease
Authors: Radsak Markus P. , Taube Christian , Haselmayer Philipp , Tenzer Stefan , Salih Helmut R. , Wiewrodt Rainer , Buhl Roland , Schild Hansjörg
Published: November 2007

Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a systemic disease that is associated with increased serum levels of markers of systemic inflammation. The triggering receptor expressed on myeloid cells 1 (TREM-1) is a recently identified activating receptor on neutrophils, monocytes, and macrophage subsets. TREM-1 expression is upregulated by microbial products such as the toll-like receptor ligand lipoteichoic acid of Gram-positive or lipopolysaccharides of Gram-negative bacteria. In the present study, sera from 12 COPD patients (GOLD stages I–IV,FEV151±6%) and 10 healthy individuals were retrospectively analyzed for soluble TREM-1 (sTREM-1) using a newly developed ELISA. In healthy subjects, sTREM-1 levels were low (median 0.25 ng/mL, range 0–5.9 ng/mL). In contrast, levels of sTREM-1 in sera of COPD patients were significantly increased (median 11.68 ng/mL, range 6.2–41.9 ng/mL,P<.05). Furthermore, serum levels of sTREM-1 showed a significant negative correlation with lung function impairment. In summary, serum concentrations of sTREM-1 are increased in patients with COPD. Prospective studies are warranted to evaluate the relevance of sTREM-1 as a potential marker of the disease in patients with COPD.
Correlation between the Bulk Modulus and the Metallicity in Semiconductors
Authors: Al-Douri Y.
Published: November 2007

The metallicity in semiconductors with respect to energy gap alongΓ→Xis used to calculate bulk modulus and gives reasonable results in agreement to that of experimental and Cohen results.
A Tauberian Theorem with a Generalized One-Sided Condition
Authors: Çanak Ibrahim , Totur Ümit
Published: November 2007

We prove a Tauberian theorem to recover moderate oscillation of a real sequenceu=(un)out of Abel limitability of the sequence(Vn(1)(Δu))and some additional condition on the general control modulo of oscillatory behavior of integer order ofu=(un).
Expression Divergence of Tandemly Arrayed Genes in Human and Mouse
Authors: Shoja Valia , Murali T. M. , Zhang Liqing
Published: November 2007

Tandemly arrayed genes (TAGs) account for about one third of the duplicated genes in eukaryotic genomes, yet there has not been any systematic study of their gene expression patterns. Taking advantage of recently published large-scale microarray data sets, we studied the expression divergence of 361 two-member TAGs in human and 212 two-member TAGs in mouse and examined the effect of sequence divergence, gene orientation, and chromosomal proximity on the divergence of TAG expression patterns. Our results show that there is a weak negative correlation between sequence divergence of TAG members and their expression similarity. There is also a weak negative correlation between chromosomal proximity of TAG members and their expression similarity. We did not detect any significant relationship between gene orientation and expression similarity. We also found that downstream TAG members do not show significantly narrower expression breadth than upstream members, contrary to what we predict based on TAG expression divergence hypothesis that we propose. Finally, we show that both chromosomal proximity and expression correlation in TAGs do not differ significantly from their neighboring non-TAG gene pairs, suggesting that tandem duplication is unlikely to be the cause for the higher-than-random expression association between neighboring genes on a chromosome in human and mouse.
Nonlinear Vector Variational Inequality Problems for η-Pseudomonotone Maps
Authors: Farajzadeh A. P.
Published: November 2007

We consider a new class of complementarity problems for η-pseudomonotone maps and obtain an existence result for their solutions in real Hausdorff topological vector spaces. Our results extend the same previous results in this literature.
Telemedicine Facilitates CHF Home Health Care for Those with Systolic Dysfunction
Authors: Seibert Pennie S. , Whitmore Tiffany A. , Patterson Carin , Parker Patrick D. , Otto Caitlin , Basom Jean , Whitener Nichole , Zimmerman Christian G.
Published: November 2007

An estimated 5 million Americans have congestive heart failure (CHF) and one in five over the age of 40 will develop CHF. There are numerous examples of CHF patients living beyond the years normally expected for people with the disease, usually attributed to taking an active role in disease management. A relatively new alternative for CHF outpatient care is telemedicine and e-health. We investigated the effects of a 6-week in-home telemedicine education and monitoring program for those with systolic dysfunction on the utilization of health care resources. We also measured the effects of the unit 4.5 months after its removal (a total of 6 months post introduction of the unit into the home). Concurrently, we assessed participants' perceptions of the value of having a telemedicine unit. Participants in the telemedicine group reported weighing more times a week with less variability than did the control group. Telemedicine led to a reduction in physician and emergency department visits and those in the experimental group reported the unit facilitating self-care, though this was not significantly different from the control group (possibly due to small sample size). These findings suggest a possibility for improvement in control of CHF when telemedicine is implemented. Our review of the literature also supports the role of telemedicine in facilitating home health care and self-management for CHF patients. There are many challenges still to be addressed before this potential can be reached and further research is needed to identify opportunities in telemedicine.
Metallocene Antimalarials: The Continuing Quest
Authors: Blackie Margaret A. L. , Chibale Kelly
Published: November 2007

Over the last decade, a significant body of research has been developed around the inclusion of a metallocene moiety into known antimalarial compounds. Ferroquine is the most successful of these compounds. Herein, we describe our contribution to metallocene antimalarials. Our approach has sought to introduce diversity sites in the side chain of ferroquine in order to develop a series of ferroquine derivatives. The replacement of the ferrocenyl moiety with ruthenocene has given rise to ruthenoquine and a modest series of analogues. The reaction of ferroquine and selected analogues with Au(PPh3)NO3, Au(C6F5)(tht), and [Rh(COD)Cl2] has resulted in a series of heterobimetallic derivatives. In all cases, compounds have been evaluated for in vitro antiplasmodial activity in both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. Preliminary structure-activity relationships have been delineated.
Collaboration between hepatic and intratumoral prodrug activation in a P450 prodrug-activation gene therapy model for cancer treatment
Authors: Ma Jie , Waxman David J.
Published: November 2007

Presently, we investigate the mechanisms whereby intratumoral expression of a cyclophosphamide-activating hepatic cytochrome P450 gene enhances therapeutic activity when cyclophosphamide is given on an every 6-day (metronomic) schedule. In P450-deficient 9L gliosarcomas grown in severe combined immunodeficient mice, metronomic cyclophosphamide substantially decreased tumor microvessel density and induced a ∼70% loss of endothelial cells that began after the second cyclophosphamide treatment. These responses were accompanied by increased expression of the endogenous angiogenesis inhibitor thrombospondin-1 in tumor-associated host cells but by decreased expression in 9L tumor cells. These antiangiogenic responses preceded tumor regression and are likely key to the therapeutic activity of metronomic cyclophosphamide. Unexpectedly, 9L/2B11 tumors, grown from 9L cells infected with retrovirus encoding the cyclophosphamide-activating P450 2B11, exhibited antiangiogenic responses very similar to 9L tumors. This indicates that the tumor endothelial cell population is well exposed to liver-activated cyclophosphamide metabolites and that intratumoral P450 confers limited additional anti–endothelial cell bystander activity. In contrast, an increase in apoptosis, which preceded the antiangiogenic response, was substantially enhanced by intratumoral P450 2B11 expression. 9L/2B11 tumor regression was accompanied by an overall loss of tumor cellularity and by substantial enlargement of remaining P450-immunoreactive tumor cells as the number of P450-positive tumor cell decreased and the P450 protein content declined with cyclophosphamide treatment. We conclude that metronomic cyclophosphamide regresses P450-expressing tumors by two independent but complementary mechanisms: increased tumor cell killing via intratumoral P450-catalyzed prodrug activation, coupled with strong antiangiogenic activity, which is primarily associated with hepatic prodrug activation. [Mol Cancer Ther 2007;6(11):2879–90]
Importance of Subtle Amnestic and Nonamnestic Deficits in Mild Cognitive Impairment: Prognosis and Conversion to Dementia
Authors: Rountree S.D. , Waring S.C. , Chan W.C. , Lupo P.J. , Darby E.J. , Doody R.S.
Published: November 2007

Background/Aims: To evaluate baseline characteristics and conversion to dementia in mild cognitive impairment (MCI) subtypes. Methods: We prospectively evaluated conversion to dementia in 106 patients with amnestic MCI (A-MCI) as defined by Petersen’s operationalized criteria on a paragraph recall task, amnestic-subthreshold MCI (AS-MCI) as defined by impairment on the ADAS-cog delayed word list recall with normal paragraph recall, nonamnestic MCI (NA-MCI) defined by a nonmemory domain, and in 27 patients with subjective memory loss who had no deficit on formal neuropsychological testing. Results: For all MCI subtypes, the 4-year conversion to dementia was 56% (14% annually) and to AD was 46% (11% annually). Conversion to AD in the A-MCI (56%) was similar to the rate in AS-MCI (50%). Conversion to AD in the A-MCI and AS-MCI combined was 56% (14% annually). Conversion to dementia in the NA-MCI was 52% (13% annually) and the majority converted to AD (62%). Conclusions: All MCI subtypes are at risk of converting to AD if the groups are carefully defined by an abnormal psychometric domain. All subtypes except subjective memory loss converted to AD at higher than expected rates. Both the A-MCI and AS-MCI subtypes had a similarly high rate of conversion to AD. The deficit on a word list recall task may develop before an abnormality on delayed paragraph recall is evident, at least in some subjects.
Bronchoalveolar Lavage plus Surfactant in a Piglet Model of Meconium Aspiration Syndrome
Authors: Colvero Mauricio Obal , Fiori Humberto Holmer , Fiori Renato Machado , Luz Jorge Hecker , de Paula Davi , Oppermann Christina , Pitrez Paulo Márcio , da Silva Vinícius Duval , Colvero Aline Pieruccini
Published: November 2007

Introduction: Meconium aspiration produces airway obstruction and surfactant inhibition. Bronchoalveolar lavage (BAL) and surfactant replacement have been proposed as treatments for the syndrome. Objective: To evaluate the effect of BAL with normal saline followed by a supplementary dose of surfactant in a piglet model of meconium aspiration syndrome. Methods: 15 newborn piglets were used in the study. The animals were ventilated with fixed settings. After inhalation of 4 ml/kg of diluted meconium, the piglets were randomized into three groups: group I (n = 5) – tracheal aspiration without BAL; group II (n = 5) – BAL with normal saline (15 ml/kg), and group III (n = 5) – BAL with normal saline (15 ml/kg) followed by a supplementary dose of surfactant (Curosurf® 100 mg/kg). Arterial blood gas samples were obtained 30 min and 6 h after the inhalation of meconium. Results: A significant increase of PaO2 values at 6 h after treatment was only observed in group III (from 51 ± 13 to 189 ± 115 mm Hg; p = 0.04). At this time, PaO2 in group III was significantly higher compared to group II (189 ± 115 and 37 ± 11 mm Hg, respectively; p = 0.023) and showed a borderline significance when compared to group I (p = 0.066). Conclusion: BAL with normal saline followed by a supplementary dose of surfactant may improve oxygenation in an experimental piglet model of meconium aspiration syndrome.
The Search for Objective Criteria at the Limit of Viability
Authors: Bartels Dorothee B. , Poets Christian F.
Published: November 2007

Background: Defining the limit of viability among very preterm infants remains a difficult issue. A recent study suggested severity of intrauterine growth retardation as a decisive criterion, reporting very poor survival for infants born at ≤28 weeks with birth weight <2nd centile. Objective: To check whether the above criterion can be confirmed in a similar analysis of German data. Methods: Analyses were based on German population-based data from Lower Saxony, including preterm neonates (22–28 weeks) without severe congenital malformations (n = 3,453), born 1991–1999. For the definition of growth retardation postnatal (<3rd, <10th centile) and antenatal (<3rd centile) reference values were used. Results: Depending on the definition used, proportions of growth retarded infants varied considerably (4–16%). Survival rates increased from 0 to 64%, arguing against considering infants <28 weeks’ GA as a homogenous group with regard to their odds for survival. Conclusion: There is an association between severity of growth retardation and VLBW mortality in general, but overinterpreting results from single studies may lead to dangerous conclusions. Data from preterm infants should be stratified by week of gestation.
Influence of Prematurity on Postnatal Maturation of Heart Rate and Arterial Pressure Responses to Hypoxia in Lambs
Authors: Pladys Patrick , Arsenault Julie , Reix Philippe , Rouillard Lafond Joelle , Moreau-Bussière François , Praud Jean-Paul
Published: November 2007

Background: While hypoxic events with bradycardias are a frequent occurrence during the first weeks of life in preterm infants, the impact of preterm birth on maturation of the cardiovascular response to hypoxia in early postnatal life is unknown. Objectives: In the present study, we tested the hypothesis that preterm birth influences postnatal maturation of cardiovascular responses to hypoxia. Methods: 6 preterm lambs (term 132 days, birth weight 2.9 kg) and 6 full-term lambs (term 147 days, birth weight 4.3 kg) were studied without sedation on days 3, 7, 14, 21 and 28 during acute, steady-state hypoxia (FIO2 = 0.08, 15 min). Results: Results show that full-term lambs increased their heart rate (HR) in response to hypoxia from the first day of life, with no postnatal maturation thereafter. In preterm lambs, HR did not change before day 14 and the full-term-like response was not acquired before 2 weeks after theoretical term. In both groups, mean arterial pressure tended to decrease below baseline, but the amplitude of variations remained of small magnitude. Conclusion: The present results bring unique evidence that preterm birth is associated with a blunted heart response to steady-state hypoxia during the first postnatal week and a delay in the maturation of HR response.
Quantitative Assessment of the Degree of Ductal Steal Using Celiac Artery Blood Flow to Left Ventricular Output Ratio in Preterm Infants
Authors: El-Khuffash Afif , Higgins Mary , Walsh Kevin , Molloy Eleanor J.
Published: November 2007

Background: Determining the significance of a patent ductus arteriosus (PDA) remains difficult in preterm neonates and current echocardiographic markers give little information about ductal steal. We hypothesized that the relationship between celiac artery flow (CAF) and left ventricular output (LVO) in the presence of a PDA may determine haemodynamic significance. Objectives: To examine CAF to LVO ratio (CAF:LVO) in the presence and the absence of a PDA in preterm neonates, and to compare CAF:LVO to current echocardiographic markers of a significant PDA. Methods: This was a prospective observational study of neonates <1,500 g. Echocardiography was performed at 12 h and day 3. PDA, LVO and CAF were measured by echocardiography. The infants were divided into those who developed a significant PDA (PDA >1.4 mm and left atrial to aortic ratio >1.5 on day 3) and controls. A further assessment was carried out following successful PDA treatment with ibuprofen or surgical ligation. Results: A total of 33 infants were enrolled. 19 infants had a PDA (median gestation 27 weeks, birth weight 915 g), and 14 controls (gestation 28.7 weeks, birth weight 1,110 g). At 12 h, there was no difference in CAF, LVO or CAF:LVO. On day 3, there was a significant difference in CAF:LVO between PDA versus control groups. CAF:LVO significantly correlated with conventional markers of ductal significance. A CAF:LVO value of 0.10 had a sensitivity of 93% and a specificity of 78% for the presence of a significant PDA. Following successful PDA treatment CAF:LVO returned to levels similar to controls. Conclusion: CAF:LVO may be used to determine which PDA warrants treatment and serve as a marker of treatment success. Trials are needed to correlate CAF:LVO with outcome and the impact of basing PDA treatment on this ratio.
Intra-Individual Consistency in the Quality of Neonatal General Movements
Authors: Mutlu Akmer , Einspieler Christa , Marschik Peter B. , Livanelioglu Ayse
Published: November 2007

Background:The qualitative assessment of general movements (GMs) proved to be a highly sensitive and specific diagnostic tool for the assessment of the integrity of the young nervous system. It is essential that the quality of GMs remains consistent in an individual during a given recording at a certain date. Objectives:The aim of the study was to investigate the intra-individual consistency of the quality of GMs during one recording. Methods: 39 preterm infants were recorded at least twice; some were recorded three times. In all, 88 recordings were available but three recordings were excluded due to frequent crying, seizures or hypokinesia. Three scorers assessed 2–3 sequences of these 85 GM recordings.Results:The inter-scorer agreement was high (ĸ 0.85–0.94). Intra-individual consistency revealed a ĸ of 0.90 with a 95% CI (0.51, 1.00) for preterm GMs, 0.96 with a 95% CI (0.57, 1.00) for writhing GMs, and 0.92 with a 95% CI (0.53, 1.00) for fidgety GMs. Conclusions:The individual quality of GMs remains consistent for a neonate or young infant at a certain date.
National Pathfinder Survey of 12-Year-Old Children’s Oral Health in Italy
Authors: Campus G. , Solinas G. , Cagetti M.G. , Senna A. , Minelli L. , Majori S. , Montagna M.T. , Reali D. , Castiglia P. , Strohmenger L.
Published: November 2007

No recent data on the experience of caries among Italian 12-year-olds are available. In 2004, an epidemiological survey called ‘National Pathfinder among Children’s Oral Health in Italy’ was promoted and carried out. This study reports the actual oral health status of Italian 12-year-olds according to gender, residence area and geographical distribution. Clinical examinations were carried out from March 2004 to April 2005, according to WHO criteria, and included dental caries (decay at the dentinal lesion level) and Community Periodontal Index (CPI). 5,342 children (2,670 males, 2,672 females) were examined by 7 ad hoc calibrated raters. Dental caries experience was found in 43.1% (95% CI 41.8–44.4%) of the study population. The mean DMFT score was 1.09 (95% CI 0.98–1.21). Significant differences (p < 0.05) were observed among geographical sections for DT, FT and DMFT. An inverse relationship was observed between mean DMFT and gross national product per capita (p < 0.001). Gingival bleeding was observed in 23.8% of children, while 28.7% had calculus. Significant differences in CPI scores among sections were found throughout the sample in both males and females (p < 0.001). Over the past two decades, mean DMFT fell from over 5 to its present level, halving every decade; consequently, the recorded level of dental caries has become aligned with that in other Western European countries. Nevertheless, differences in DMFT values remain between children from different socioeconomic backgrounds.
Effects of Sevelamer and Calcium-Based Phosphate Binders on Lipid and Inflammatory Markers in Hemodialysis Patients
Authors: Shantouf Ronney , Budoff Matthew J. , Ahmadi Naser , Tiano Jima , Flores Ferdinand , Kalantar-Zadeh Kamyar
Published: November 2007

Introduction: Cardiovascular disease accounts for almost half of all deaths in individuals with chronic kidney disease stage 5 despite advances in both dialysis treatment and cardiology. A combination of lipid-lowering and anti-inflammatory effects along with avoidance of hypercalcemia should be taken into account when choosing phosphorus binders for maintenance hemodialysis (MHD) patients. Methods: We examined the association of sevelamer versus calcium-based phosphorus binders with lipid profile, inflammatory markers including C-reactive protein (CRP), and mineral metabolism in MHD patients who participated in the Nutritional and Inflammatory Evaluation of Dialysis Patients (NIED) study from October 2001 to July 2005. Results: Of the 787 MHD patients in the NIED study, 697 were on either sevelamer, a calcium-based binder, or both and eligible for this study. We compared the groups based on taking sevelamer monotherapy (n = 283) or calcium binder monotherapy (n = 266) for serum phosphate control. There were no differences between the groups on dialysis vintage. There were significant differences in age, serum calcium and phosphorus levels, as well as intact parathyroid hormone levels. Using a logistic regression models, the sevelamer group had a higher odds of serum CRP <10 mg/l [odds ratio (OR): 1.06, 95% CI: 1.02–1.11] and LDL cholesterol <70 mg/dl (OR: 1.33, 95% CI: 1.19–1.47) when compared to the calcium binder group independent of age, vintage, body mass index, statin use or other variables. Conclusion: The improvements in multiple surrogate markers of inflammation and lipids in the NIED study make sevelamer a promising therapy for treatment in MHD patients with high risk of cardiovascular disease and mortality.
Late-Outgrowth Endothelial Cells Attenuate Intimal Hyperplasia Contributed by Mesenchymal Stem Cells After Vascular Injury
Authors: Wang Chao-Hung , Cherng Wen-Jin , Yang Ning-I , Kuo Li-Tang , Hsu Chia-Ming , Yeh Hung-I , Lan Yii-Jenq , Yeh Chi-Hsiao , Stanford William L.
Published: November 2007

Objectives—

Mesenchymal stem cells (MSCs) are one of a number of cell types undergoing extensive investigation for cardiac regeneration therapy. It has not yet been determined whether this cell therapy also substantially contributes to vascular remodeling of diseased vessels.

Methods and Results—

Human MSCs and a variety of progenitor and vascular cells were used for in vitro and in vivo experiments. Wire-induced vascular injury mobilized MSCs into the circulation. Compared with human aortic smooth muscle cells, MSCs exhibited a 2.8-fold increase in the adhesion capacity in vitro (
P
<0.001) and a 6.3-fold increase in vivo (
P
<0.001). In all animal models, a significant amount of MSCs contributed to intimal hyperplasia after vascular injury. MSCs were able to differentiate into cells of endothelial or smooth muscle lineage. Coculture experiments demonstrated that late-outgrowth endothelial cells (OECs) guided MSCs to differentiate toward an endothelial lineage through a paracrine effects. In vivo, cell therapy with OECs significantly attenuated the thickness of the neointima contributed by MSCs (intima/media ratio, from 3.2±0.4 to 0.4±0.1,
P
<0.001).

Conclusions—

Tissue regeneration therapy with MSCs or cell populations containing MSCs requires a strategy to attenuate the high potential of MSCs to develop intimal hyperplasia on diseased vessels.
Prothrombotic Effects of Fibronectin Isoforms Containing the EDA Domain
Authors: Chauhan Anil K. , Kisucka Janka , Cozzi Maria R. , Walsh Meghan T. , Moretti Federico A. , Battiston Monica , Mazzucato Mario , De Marco Luigi , Baralle Francisco E. , Wagner Denisa D. , Muro Andrés F.
Published: November 2007

Objective—

Fibronectin (FN) plays an important role in the formation of stable arterial thrombi at the site of vascular injury. FN containing Extra Domain A (EDA
+
FN) is absent from normal plasma, but elevated plasma levels of EDA
+
FN are found in several pathological conditions. We hypothesized that EDA
+
FN plays a special role in thrombosis.

Methods and Results—

We used mouse strains constitutively including (EDA
+/+
) or excluding (EDA
−/−
) the EDA domain in all tissues and plasma. Using a flow chamber and the ferric-chloride injury model we found that EDA
+
FN accelerates thrombosis both in vitro and in vivo at arterial shear rates. In EDA
+/+
mice thrombi (>30 μm) grew faster when compared with EDA
WT/WT
(6.6±0.2 minutes versus 8.3±0.6 minutes,
P
<0.05) and the mean vessel occlusion time was shorter (9.9±0.4 minutes versus 14.6±1.7 minutes,
P
<0.05). However, the presence of EDA
+
FN affected neither single platelet adhesion to subendothelium nor thrombosis in veins. In addition, the mortality rate of EDA
+/+
mice after collagen/epinephrine infusion was twice that of EDA
WT/WT
or EDA
−/−
mice.

Conclusions—

Our findings reveal that EDA
+
FN has prothrombotic activity, and its presence in plasma may worsen pathological conditions in which this form is elevated.
Inflammation, Statin Therapy, and Risk of Stroke After an Acute Coronary Syndrome in the MIRACL Study
Authors: Kinlay Scott , Schwartz Gregory G. , Olsson Anders G. , Rifai Nader , Szarek Michael , Waters David D. , Libby Peter , Ganz Peter
Published: November 2007

Objective—

Patients with acute coronary syndromes have an increased risk of stroke. We measured markers of inflammation in the MIRACL study, a randomized trial of atorvastatin versus placebo in acute coronary syndromes, to assess the relationship of inflammation to stroke.

Methods and Results—

Baseline C-reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) were collected in 2926 (95%) subjects. Baseline markers were related to stroke risk over the 16 weeks of the study. Subjects who subsequently experienced a stroke had higher CRP (27.5 versus 10.2 mg/L,
P
=0.0032), SAA (30.5 versus 16.0 mg/L,
P
=0.031), IL-6 (11 231 versus 6841 pg/L,
P
=0.004), and troponin (6.03 versus 3.19 ng/mL
P
=0.0032). The risk of stroke was related to greater CRP, SAA, and IL-6 in the placebo group only. Similarly, there was a graded increase in risk of stroke across quartiles of inflammatory markers in the placebo patients only.

Conclusions—

In acute coronary syndromes, the early risk of stroke relates to both heightened inflammation and size of myocardial necrosis. Treatment with atorvastatin abrogated the risk associated with elevated markers of inflammation in this study, a finding that provides a novel rationale for the use of statins in acute coronary syndromes.
Differential Impact of Age, Sex, and Hypertension on Aortic Atherosclerosis
Authors: Oyama Noriko , Gona Philimon , Salton Carol J. , Chuang Michael L. , Jhaveri Rahul R. , Blease Susan J. , Manning Anya R. , Lahiri Marc , Botnar René M. , Levy Daniel , Larson Martin G. , O’Donnell Christopher J. , Manning Warren J.
Published: November 2007

Objective—

The purpose of this study was to investigate the impact of age, sex, and hypertension (HTN) on aortic atherosclerotic burden using cardiovascular MRI (CMR) in a free-living longitudinally followed cohort.

Methods and Results—

1763 participants (829 M and 934 F; 38 to 88 years of age) of the Framingham Heart Study Offspring cohort underwent CMR of the thoracoabdominal aorta using an ECG-gated 2D T2-weighted black-blood sequence. Of these, 1726 subjects (96%) with interpretable CMR were characterized by sex, age-quartile, and presence or absence of HTN and clinical cardiovascular disease (CVD). Aortic plaque prevalence and volume increased with increasing age in both sexes. For the nonhypertensive (no-HTN) group, plaque was identified in 702 (46%) with greater prevalence in women than in men (
P
<0.006). HTN was associated with greater aortic plaque burden (
P
<0.02). The 200 subjects with clinical CVD had greater plaque burden than subjects without CVD (
P
<0.0001).

Conclusions—

In this free-living longitudinally followed cohort, subclinical aortic atherosclerosis was seen in nearly half of subjects and increased with advancing age. HTN was associated with increased aortic plaque burden. Among no-HTN subjects, women had greater plaque burden than men. These data suggest that subclinical atherosclerosis is more common in no-HTN women and emphasize the importance of focusing on preventive measures in both sexes.
Increased Smooth Muscle Cell Activation and Neointima Formation in Response to Injury in AIF-1 Transgenic Mice
Authors: Sommerville Laura J. , Kelemen Sheri E. , Autieri Michael V.
Published: November 2007

Objective—

Allograft Inflammatory Factor-1 (AIF-1) is a calcium binding scaffold protein which is rapidly induced in vascular smooth muscle cells (VSMCs) in response to injury and inflammation. A transgenic mouse in which AIF-1 expression was driven by a VSMC-specific SM22α promoter was generated to establish a direct relationship between AIF-1 expression and intimal hyperplasia.

Methods and Results—

Morphological analysis of partially ligated carotid artery demonstrate a significant increase in neointimal area of AIF-1 Tg versus wild-type mice (569±64 um versus 256±49um,
P
=0.004). Immunohistochemistry using antibody to the proliferation marker Ki-67 show a significantly greater number of proliferating cells in the AIF-1 Tg lesion compared with wild-type arteries (10.6%±1.0 versus 3.6%±.9,
P
=0.0007). AIF-1 Tg arteries also had a greater number of cells with activated signal transduction kinase p38 (55.4%±7.0 versus 22.6%±5.4,
P
=0.002) and PAK1 (67.5%±6.7 versus 35.3%±10.2,
P
=0.02) compared with wild-type. Cultured VSMCs explanted from AIF-1 Tg proliferate (55.5±3.6×10
3
versus 37.2±2.0×10
3
cells/mL,
P
=0.0001) and migrate more rapidly (39.2±3.2 versus 17.1±1.5 VSMCs per HPF,
P
=0.0003) than wild-type, and have significantly greater levels of activated p38 and PAK1 than did VSMCs from wild-type littermates (
P
<0.05).

Conclusions—

These data indicate that AIF-1 expression results in increased signal transduction, neointimal formation, and VSMC proliferation in injured mouse carotid arteries.
Regulation of Endothelial Cell Proliferation by Primary Monocytes
Authors: Schubert Shai Y. , Benarroch Alejandro , Ostvang Janne , Edelman Elazer R.
Published: November 2007

Objective—

Endothelial cell–monocyte cross talk is essential for vascular repair. Monocytes colocalize with endothelial cells forming a complex set of interactions distinct from the growth promoting cytokines secreted by differentiated macrophages. In the present work we examined the growth regulation and in vitro wound repair early after binding of monocytes to endothelial cells.

Methods and Results—

After direct contact with primary unactivated monocytes, endothelial cells enter S-phase through a mechanism mediated in part by contact-dependent activation of endothelial Met as demonstrated by siRNA silencing of Met, neutralizing antibodies for hepatocyte growth factor and Met as well as by specific inhibition of Met by the Met kinase inhibitor SU11274. Monocytes robustly promote endothelial cell proliferation and migration into a wounded endothelial monolayer. Monocyte-induced endothelial cell proliferation is accompanied by prolonged extracellular signal-regulated kinase (ERK) activation and is inhibited by the specific ERK inhibitor PD98059. The contact-mediated effect of monocytes is specific to endothelial cells and does not occur with vascular smooth muscle cells. Interestingly, although Flk1 is activated by monocytes, the proliferative effect of monocytes reported here is minimally mediated by Flk1 signaling.

Conclusions—

These results suggest that the early interaction between endothelial cells and monocytes is critical for the regulation of endothelial cell proliferation. This complex regulation is mediated in part by contact-dependent Met and ERK phosphorylation. These findings add to a broader set of leukocyte-endothelial contact mediated signals that together regulate endothelial function in health and disease.
15-Lipoxygenase-1 Prevents Vascular Endothelial Growth Factor A– and Placental Growth Factor–Induced Angiogenic Effects in Rabbit Skeletal Muscles via Reduction in Growth Factor mRNA Levels, NO Bioactivity, and Downregulation of VEGF Receptor 2 Expression
Authors: Viita Helena , Markkanen Johanna , Eriksson Emmi , Nurminen Markku , Kinnunen Kati , Babu Mohan , Heikura Tommi , Turpeinen Sanna , Laidinen Svetlana , Takalo Teemu , Ylä-Herttuala Seppo
Published: November 2007

Human 15-lipoxygenase-1 (15-LO-1) is an oxidizing enzyme capable of producing reactive lipid hydroperoxides. 15-LO-1 and its products have been suggested to be involved in many pathological conditions, such as inflammation, atherogenesis, and carcinogenesis. We used adenovirus-mediated gene transfers to study the effects of 15-LO-1 on vascular endothelial growth factor (VEGF)-A
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– and placental growth factor (PlGF)-induced angiogenesis in rabbit skeletal muscles. 15-LO-1 significantly decreased all angiogenic effects induced by these growth factors, including capillary perfusion, vascular permeability, vasodilatation, and an increase in capillary number. The effects are attributable to the reduction in the amount of VEGF-A
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and PlGF transcripts by 15-LO-1, resulting in reduced protein expression. The most likely mediator of the VEGF family–induced capillary vasodilatation is nitric oxide (NO), which is produced by NO synthases. Endothelial NO synthase protein expression and NO synthase activity were significantly induced by VEGF-A
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, and these inductions were reduced by 15-LO-1. VEGF-A
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induces its angiogenic effects primarily via vascular endothelial growth factor receptor (VEGFR)2, and also PlGF mediates angiogenic signaling via VEGFR2, even though it binds to VEGFR1. VEGFR2 expression is induced by peroxisome proliferator-activating receptor γ. We showed by quantitative RT-PCR and immunohistochemistry that expression of endogenous rabbit peroxisome proliferator-activating receptor γ and VEGFR2 were significantly increased in the growth factor–transduced muscles, but these inductions were efficiently prevented by 15-LO-1. In conclusion, the results suggest that expression of 15-LO-1 has an efficient antiangiogenic effect in vivo via reduction in growth factor mRNA levels, NO bioactivity, and VEGFR2 expression.
Atrial Natriuretic Peptide Inhibits Transforming Growth Factor β–Induced Smad Signaling and Myofibroblast Transformation in Mouse Cardiac Fibroblasts
Authors: Li Peng , Wang Dajun , Lucas Jason , Oparil Suzanne , Xing Dongqi , Cao Xu , Novak Lea , Renfrow Matthew B. , Chen Yiu-Fai
Published: November 2007

This study tested the hypothesis that activation of atrial natriuretic peptide (ANP)/cGMP/protein kinase G signaling inhibits transforming growth factor (TGF)-β1–induced extracellular matrix expression in cardiac fibroblasts and defined the specific site(s) at which this molecular merging of signaling pathways occurs. Left ventricular hypertrophy and fibrosis, collagen deposition, and myofibroblast transformation of cardiac fibroblasts in response to pressure overload by transverse aortic constriction were exaggerated in ANP-null mice compared with wild-type controls. ANP and cGMP inhibited TGF-β1–induced myofibroblast transformation, proliferation, collagen synthesis, and plasminogen activator inhibitor-1 expression in cardiac fibroblasts isolated from wild-type mice. Following pretreatment with cGMP, TGF-β1 induced phosphorylation of Smad3, but the resultant pSmad3 could not be translocated to the nucleus. pSmad3 that had been phosphorylated with recombinant protein kinase G-1α was analyzed by use of Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and ion trap tandem mass spectrometry. The analysis revealed phosphorylation of Ser309 and Thr388 residues, sites distinct from the C-terminal Ser423/425 residues that are phosphorylated by TGF-β receptor kinase and are critical for the nuclear translocation and down-stream signaling of pSmad3. These results suggest that phosphorylation of Smad3 by protein kinase G is a potential molecular mechanism by which activation of ANP/cGMP/protein kinase G signaling disrupts TGF-β1–induced nuclear translocation of pSmad3 and downstream events, including myofibroblast transformation, proliferation, and expression of extracellular matrix molecules in cardiac fibroblasts. We postulate that this process contributes to the antifibrogenic effects of the natriuretic peptide in heart.
Angiotensin II–Mediated Oxidative DNA Damage Accelerates Cellular Senescence in Cultured Human Vascular Smooth Muscle Cells via Telomere-Dependent and Independent Pathways
Authors: Herbert Karl E. , Mistry Yogita , Hastings Richard , Poolman Toryn , Niklason Laura , Williams Bryan
Published: November 2007

Angiotensin II (Ang II) induces reactive oxygen species (ROS) production by human vascular smooth muscle cells (hVSMCs). ROS have been implicated in the development of both acute stress-induced premature senescence (SIPS) and chronic replicative senescence. Global oxidative DNA damage triggers SIPS and telomere DNA damage accelerates replicative senescence, both mediated via p53. This study tests the hypothesis that DNA is an important target for Ang II–induced ROS leading to senescence via telomere-dependent and independent pathways. DNA damage was quantified using the Comet assay, telomere DNA length by Southern blotting and hVSMC senescence by senescence-associated β-galactosidase staining. Exposure to Ang II increased DNA damage in hVSMCs within 4 hours. Inhibition by an AT
1
receptor antagonist (losartan metabolite: E3174) or catalase, confirmed that Ang II–induced DNA damage was AT
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receptor-mediated, via the induction of ROS. Acute exposure to Ang II resulted in SIPS within 24 hours that was prevented by coincubation with E3174 or catalase. SIPS was associated with increased p53 expression but was not dependent on telomere attrition because overexpression of human telomerase did not prevent Ang II–induced SIPS. Exposure to Ang II over several population doublings accelerated the rate of telomere attrition (by >2-fold) and induced premature replicative senescence of hVSMCs—an effect that was also attenuated by E3174 or catalase. These data demonstrate that Ang II–induced ROS-mediated DNA damage results in accelerated biological aging of hVSMCs via 2 mechanisms: (1) Acute SIPS, which is telomere independent, and (2) accelerated replicative senescence which is associated with accelerated telomere attrition.
Endoplasmic Reticulum Stress in the Heart
Authors: Glembotski Christopher C.
Published: November 2007

Over the last decade, it has become clear that the accumulation of misfolded proteins contributes to a number of neurodegenerative, immune, and endocrine pathologies, as well as other age-related illnesses. Recent interest has focused on the possibility that the accumulation of misfolded proteins can also contribute to vascular and cardiac diseases. In large part, the misfolding of proteins takes place during synthesis on free ribosomes in the cytoplasm or on endoplasmic reticulum ribosomes. In fact, even under optimal conditions, ≈30% of all newly synthesized proteins are rapidly degraded, most likely because of improper folding. Accordingly, stresses that perturb the folding of proteins during or soon after synthesis can lead to the accumulation of misfolded proteins and to potential cellular dysfunction and pathological consequences. To avert such outcomes, cells have developed elaborate protein quality-control systems for detecting misfolded proteins and making appropriate adjustments to the machinery responsible for protein synthesis and/or degradation. Important contributors to protein quality control include cytosolic and organelle-targeted molecular chaperones, which help fold and stabilize proteins from unfolding, and the ubiquitin proteasome system, which degrades terminally misfolded proteins. Both of these systems play important roles in cardiovascular biology. The focus of this review is the endoplasmic reticulum stress response, a protein quality-control and signal-transduction system that has not been well studied in the context of cardiovascular biology but that could be important for vascular and cardiac health and disease.
The Histone Demethylase, Jmjd1a, Interacts With the Myocardin Factors to Regulate SMC Differentiation Marker Gene Expression
Authors: Lockman Kashelle , Taylor Joan M. , Mack Christopher P.
Published: November 2007

We and others have previously shown that the myocardin transcription factors play critical roles in the regulation of smooth muscle cell (SMC) differentiation marker gene expression. In a yeast 2-hybrid screen for proteins that interact with myocardin-related transcription factor-A (MRTF-A), we identified the histone 3 lysine 9 (H3K9)-specific demethylase, Jmjd1a. GST pull-down assays demonstrated that Jmjd1a bound all 3 myocardin family members, and further mapping studies showed that the jumonjiC domain of Jmjd1a was sufficient to mediate this interaction. Overexpression of Jmjd1a in multipotential 10T1/2 cells decreased global levels of di-methyl H3K9, stimulated the SM α-actin and SM22 promoters, and synergistically enhanced MRTF-A– and myocardin-dependent transactivation. Using chromatin immunoprecipitation assays, we also demonstrated that TGF-β–mediated upregulation of SMC differentiation marker gene expression in 10T1/2 cells was associated with decreased H3K9 dimethylation at the CArG-containing regions of the SMC differentiation marker gene promoters. Importantly, knockdown of Jmjd1a in 10T1/2 cells and primary rat aortic SMCs by retroviral delivery of siRNA attenuated TGF-β–induced upregulation of endogenous SM myosin heavy chain expression. These effects were concomitant with increased H3K9 dimethylation at the SMC differentiation marker gene promoters and with inhibition of MRTF-A–dependent transactivation of the SMC-specific transcription. These results suggest, for the first time, that SMC differentiation marker gene expression is regulated by H3K9 methylation and that the effects of the myocardin factors on SMC-specific transcription may involve the recruitment of Jmjd1a to the SMC-specific promoters.
Playback Theatre in Cuba: The Politics of Improvisation and Free Expression
Authors: Meer Laurie Frederik
Published: November 2007

To perform Playback Theatre effectively, practitioners learn the language of their hosts, live in the same dwellings, eat the same food, and take part in daily activities. Most importantly, Playbackers listen to stories and play these back. Meer's anthropological research in Cuba has been to locate an essential Cuban "we." She finds that her work and Playback are similar in motivation and mission, a teatro comunitario.
The Spatiotemporal Dialectic of Estrangement
Authors: Robinson Douglas
Published: November 2007

In 1935 in Moscow, Mei Lanfang famously showed Brecht (and others) some gestures of classic Chinese theatre. This, Brecht said, was the source of his theory of “alienation.” Was it ethnocentric for Brecht to assume that the feeling of strangeness he experienced watching Mei Lanfang was intended by Mei? Can one talk about the Verfremsdungeffkt at all without generalizing from audience response to artist intention, or from artist intention to audience response?
Notes on the German Theatre Crisis
Authors: Hughes David Ashley
Published: November 2007

The early 1990s, with the collapse of the German Democratic Republic and the reunification of Germany, resulted in the most radical shake-up of German theatre since 1933. German theatre remains in a state of crisis, haunted by constant threats of cutbacks and closures. What is this German “theatre crisis” from the macroeconomic, political, and social perspectives? How might it be mitigated?
Dicking Around with Radiohole: Toward Hyperreal Performance and Criticism
Authors: Luber Steve
Published: November 2007

Reappropriating the iconography of “America” as portrayed in Melville's Moby-Dick, the New York-based Radiohole offers in Fluke what Steve Luber dubs a hyperreal performance. The hyperreal is also what happened to Sara Brady when she rode through Dublin with the international trio Rimini Protokoll as they reimagined the journey as a trek from Bulgaria to Ireland. The last Critical Act takes place in Tangier where Khalid Amine found Zoubeir Ben Bouchta's Lalla J'mila a negotiation of the terrains of law, gender, and “place-specific” theatre.
Cargo Sofia: A Bulgarian Truck Ride through Dublin
Authors: Brady Sara
Published: November 2007

Reappropriating the iconography of “America” as portrayed in Melville's Moby-Dick, the New York-based Radiohole offers in Fluke what Steve Luber dubs a hyperreal performance. The hyperreal is also what happened to Sara Brady when she rode through Dublin with the international trio Rimini Protokoll as they reimagined the journey as a trek from Bulgaria to Ireland. The last Critical Act takes place in Tangier where Khalid Amine found Zoubeir Ben Bouchta's Lalla J'mila a negotiation of the terrains of law, gender, and “place-specific” theatre.
Performing Gender on the Tremulous Moroccan Body: Zoubeir Ben Bouchta's Lalla J'mila
Authors: Amine Khalid
Published: November 2007

Reappropriating the iconography of “America” as portrayed in Melville's Moby-Dick, the New York-based Radiohole offers in Fluke what Steve Luber dubs a hyperreal performance. The hyperreal is also what happened to Sara Brady when she rode through Dublin with the international trio Rimini Protokoll as they reimagined the journey as a trek from Bulgaria to Ireland. The last Critical Act takes place in Tangier where Khalid Amine found Zoubeir Ben Bouchta's Lalla J'mila a negotiation of the terrains of law, gender, and “place-specific” theatre.
Performing Visibility: Freaknic and the Spatial Politics of Sexuality, Race, and Class in Atlanta
Authors: Thompson Krista A.
Published: November 2007

During the late 1990s, participants in Freaknic, the annual black college spring break gathering, were greeted by the Atlanta police in riot gear. Defying the police, women gave impromptu performances, sometimes stripping for participants' cameras. Thompson shows how these performances were a response not only to the city's treatment of Freaknic but also to Atlanta's long history of using force to control race, gender, and class.