bluuebunny/crossref_metadata_2025 huggingface dataset:
C242T Polymorphism of NADPH Oxidase p22phox and Recurrence of Cardiovascular Events in Coronary Artery Disease
Authors: Arca Marcello , Conti Beatrice , Montali Anna , Pignatelli Pasquale , Campagna Filomena , Barillà Francesco , Tanzilli Gaetano , Verna Roberto , Vestri Annarita , Gaudio Carlo , Violi Francesco
Published: February 2008

Objectives—

The common C242T polymorphism in the gene for the p22phox subunit of NADPH oxidase has been reported to be negatively associated with oxidative stress, but whether it confers prognostic information is not yet clear.

Methods and Results—

The incidence of major adverse cardiovascular events (MACE) were determined in 237 patients with coronary stenosis during a median follow-up of 7.8 years. The
p22phox
genotypes were evaluated in 213 patients (89.9%) by polymerase chain reaction and
Rsa
I. digestion. Plasma levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker of oxidative stress, were also measured. In the univariate analysis, patients with CT/TT genotypes showed reduced recurrence of cardiovascular deaths, nonfatal MI, and revascularization procedures compared with homozygous carriers of the C allele. After controlling for confounders, a significantly lower risk of new revascularization procedures (HR=0.31, 95% CI 0.12 to 0.70;
P
=0.014) remained associated with the T allele. The Kaplan–Meier analysis showed a longer survival free from fatal and nonfatal MI in carriers of T allele (
P
<0.001). The presence of the 242T allele was associated with significantly reduced plasma concentrations of 8-OHdG.

Conclusions—

The 242T allele was a predictor of lower risk of recurrence of cardiovascular events in high-risk patients and was associated with reduced systemic oxidative stress.
Angiotensin II Type 1 Receptor 1166C Polymorphism Is Associated With Abdominal Aortic Aneurysm in Three Independent Cohorts
Authors: Jones Gregory T. , Thompson Andrew R. , van Bockxmeer Frank M. , Hafez Hany , Cooper Jackie A. , Golledge Jonathan , Humphries Stephen E. , Norman Paul E. , van Rij Andre M.
Published: February 2008

Objectives—

Although polymorphic variations in genes of the RAS system have previously been associated with susceptibility to AAA, such studies have been significantly limited by small sample sizes. This study was undertaken, using the largest case series yet reported, to determine whether common genetic variants of the RAS are associated with either susceptibility or severity of AAA.

Methods and Results—

The frequencies of 4 common genetic variants of genes related to the renin-angiotensin system were investigated in 3 geographically distinct, but ethnically similar, case-control cohorts, resulting in comparison of 1226 AAA cases with 1723 controls. In all 3 the
AGTR1
1166C allele was significantly more common in AAA patients than controls (overall adjusted OR 1.60, 95% CI 1.32 to 1.93,
P
=1.1×10
−6
). Overall, the
ACE
ID genotype was associated with AAA (OR 1.33, 95% CI 1.06 to 1.67,
P
<0.02). The
AGT
268T allele appeared to have an epistatic effect on large aneurysm size.

Conclusion—

This study has identified a strong and repeated association between the AGTR1 1166C allele and susceptibility to AAA, and a weaker effect associated with the ACE deletion allele, in 3 geographically distinct, but ethnically similar, case-control cohorts. This study highlights the key role of the RAS in AAA and emphasizes the need for replication and validation of results in suitable independent cohorts.
Role for Staphylococci in Misguided Thrombus Resolution of Chronic Thromboembolic Pulmonary Hypertension
Authors: Bonderman Diana , Jakowitsch Johannes , Redwan Bassam , Bergmeister Helga , Renner Maria-Klara , Panzenböck Heidi , Adlbrecht Christopher , Georgopoulos Apostolos , Klepetko Walter , Kneussl Meinhard , Lang Irene M.
Published: February 2008

Objective—

Acute pulmonary emboli usually resolve within 6 months. However, in 0.1% to 3.8% of cases thrombus transforms into fibrous masses. If vascular obstruction is severe, the resulting condition is chronic thromboembolic pulmonary hypertension (CTEPH). Patients who carry ventriculo-atrial (VA-) shunts for the treatment of hydrocephalus and report a history of shunt infection are at an increased risk for CTEPH. Because CTEPH lacks traditional plasmatic risk factors for venous thromboembolism, we hypothesized that delayed thrombus resolution rather than abnormal coagulation is important, and that bacterial infection would be important for this misguidance.

Methods and Results—

Human CTEPH thromboemboli were harvested during pulmonary endarterectomy. The effects of Staphylococcal infection on thrombus organization were examined in a murine model of stagnant-flow venous thrombosis. Staphylococcal DNA, but not RNA, was detected in 6 of 7 thrombi from VA shunt carriers. In the mouse model, staphylococcal infection delayed thrombus resolution in parallel with upregulation of transforming growth factor (TGF) beta and connective tissue growth factor.

Conclusions—

In the present work, we propose a mechanism of disease demonstrating that infection with Staphylococci enhances fibrotic vascular remodeling after thrombosis, resulting in misguided thrombus resolution. Thrombus infection appears to be a trigger in the evolution of CTEPH.
Plasminogen Activator Inhibitor-1 Activity in Type 2 Diabetes
Authors: Brazionis Laima , Rowley Kevin , Jenkins Alicia , Itsiopoulos Catherine , O’Dea Kerin
Published: February 2008

Background—

Plasminogen activator inhibitor (PAI)-1, a key regulator of fibrinolysis, is associated with increased risk of coronary heart disease (CHD) and is a potential therapeutic target for CHD. However, the relationship between PAI-1 and the most common diabetic microvascular complication, retinopathy, is unclear. The purpose of this study was to assess the relationship between PAI-1 activity and both retinopathy and CHD in type 2 diabetes.

Methods and Results—

We determined PAI-1 activity and both retinopathy (assessed by masked grading of 3-field retinal photographs) and CHD status (assessed by ECG and standard questionnaires) in 147 men and women with type 2 diabetes, mean age (SD) 64 (7) years, in a cross-sectional setting. Plasma PAI-1 activity was inversely associated with prevalent retinopathy (
P
=0.006) and severity of retinopathy (
P
=0.022), and was associated with lower risk of diabetic retinopathy, independent of major retinopathy risk factors (duration of diabetes and HbA1c) and determinants of PAI-1 (obesity and triglyceride level) (OR 0.74 [0.60 to 0.92],
P
=0.006). Conversely, higher plasma PAI-1 activity was independently associated with greater risk of CHD, after adjusting for the major CHD risk factors and determinants of PAI-1 (OR 1.31 [1.06 to 1.62],
P
=0.001).

Conclusion—

These data support mounting evidence that a higher PAI-1 plasma level is independently associated with a lower risk of retinopathy but a higher risk of CHD in type 2 diabetes.
A New Mechanism Involving ERK Contributes to Rosiglitazone Inhibition of Tumor Necrosis Factor-α and Interferon-γ Inflammatory Effects in Human Endothelial Cells
Authors: Lombardi Adriana , Cantini Giulia , Piscitelli Elisabetta , Gelmini Stefania , Francalanci Michela , Mello Tommaso , Ceni Elisabetta , Varano Gabriele , Forti Gianni , Rotondi Mario , Galli Andrea , Serio Mario , Luconi Michaela
Published: February 2008

Objective—

Microvascular endothelium is one of the main targets of the inflammatory response. On specific activation, endothelial cells recruit Th1-lymphocytes at the inflammatory site. We investigated the intracellular signaling mediating tumor necrosis factor (TNF)-α and interferon (IFN)-γ inflammatory response in human microvascular endothelial cells (HMEC-1) and the interfering effects of the peroxisome-proliferator-activated-receptor (PPARγ) agonist, rosiglitazone (RGZ).

Methods and Results—

TNFα and IFNγ, mainly when combined, stimulate IFNγ-inducible protein of 10 kDa (IP10) and fractalkine production evaluated by ELISA and TaqMan analyses. This effect is not only mediated by activation of the NFkB and Stat1 classic pathways, but also involves a rapid increase in phosphorylation and activation of extracellular signal-regulated kinases (ERK1/2) as measured by Western blot. RGZ interferes with TNFα and IFNγ stimulation of IP10, fractalkine, and adhesion molecule through a novel rapid mechanism which involves the blocking of ERK activation.

Conclusions—

Our findings shed new light on the mechanisms underlying the inflammatory response of microvascular endothelium and on the possible therapeutic use of RGZ in vasculopathies involving Th1-responses.
Sirt7 Increases Stress Resistance of Cardiomyocytes and Prevents Apoptosis and Inflammatory Cardiomyopathy in Mice
Authors: Vakhrusheva Olesya , Smolka Christian , Gajawada Praveen , Kostin Sawa , Boettger Thomas , Kubin Thomas , Braun Thomas , Bober Eva
Published: February 2008

Sirt7 is a member of the mammalian sirtuin family consisting of 7 genes, Sirt1 to Sirt7, which all share a homology to the founding family member, the yeast Sir2 gene. Most sirtuins are supposed to act as histone/protein deacetylases, which use oxidized NAD in a sirtuin-specific, 2-step deacetylation reaction. To begin to decipher the biological role of Sirt7, we inactivated the Sirt7 gene in mice. Sirt7-deficient animals undergo a reduction in mean and maximum lifespans and develop heart hypertrophy and inflammatory cardiomyopathy. Sirt7 mutant hearts are also characterized by an extensive fibrosis, which leads to a 3-fold increase in collagen III accumulation. We found that Sirt7 interacts with p53 and efficiently deacetylates p53 in vitro, which corresponds to hyperacetylation of p53 in vivo and an increased rate of apoptosis in the myocardium of mutant mice. Sirt7-deficient primary cardiomyocytes show a ≈200% increase in basal apoptosis and a significantly diminished resistance to oxidative and genotoxic stress suggesting a critical role of Sirt7 in the regulation of stress responses and cell death in the heart. We propose that enhanced activation of p53 by lack of Sirt7-mediated deacetylation contributes to the heart phenotype of Sirt7 mutant mice.
Hairy-Related Transcription Factors Inhibit Notch-Induced Smooth Muscle α-Actin Expression by Interfering With Notch Intracellular Domain/CBF-1 Complex Interaction With the CBF-1–Binding Site
Authors: Tang Yuefeng , Urs Sumithra , Liaw Lucy
Published: February 2008

Notch signaling regulates smooth muscle cell phenotype and is critical for vascular development. One Notch target is smooth muscle α-actin (SMA), a differentiated smooth muscle cell marker. The Notch intracellular domain (NotchICD) forms a complex with CBF-1 (C-promoter–binding factor-1) and directly induces SMA expression. Using primary human smooth muscle cells, we show that expression of the constitutive active ICD of human Notch1, Notch2, or Notch4 receptors increase SMA levels. NotchICD also induce expression of the transcriptional repressors HRT1 (Hairy-related transcription factor 1) and HRT2, in a CBF-1–dependent manner. However, unlike the activating effects of NotchICD, HRT1 or HRT2 represses basal SMA expression, and both are strong antagonists of NotchICD-induced SMA upregulation. This antagonism does not depend on histone deacetylase activity and occurs at the transcriptional level. Competitive coimmunoprecipitation experiments demonstrate that HRT does not disrupt the association of NotchICD and CBF-1, which form a complex in the presence or absence of HRTs. However, HRT suppresses NotchICD/CBF-1 binding to the SMA promoter, as measured by chromatin immunoprecipitation, and transactivation of an SMA promoter reporter spanning sequences −124/+32. SMA expression was regulated similarly following endogenous Notch activation in smooth muscle cells by coculture with endothelial cells, and this effect was also sensitive to HRT inhibition. Temporally defined HRT activity may constitute a negative feedback mechanism of Notch signaling. Our study presents a novel mechanism by which a balance between Notch signaling and HRT activity determines the expression of smooth muscle differentiation markers including SMA.
Decreased Chronic-Stage Cortical
11
C-Flumazenil Binding After Focal Ischemia-Reperfusion in Baboons
Authors: Giffard Cyril , Landeau Brigitte , Kerrouche Nacer , Young Alan R. , Barré Louisa , Baron Jean-Claude
Published: February 2008

Background and Purpose—

Although the penumbra can be saved by early reperfusion, in the rat it is consistently affected by selective neuronal loss. Mapping selective neuronal loss in the living primate would be desirable.

Methods—

Five young adult baboons underwent
15
O positron emission tomography for cerebral blood flow, cerebral oxygen consumption, and oxygen extraction fraction mapping at baseline and serially during and after 20-hour temporary middle cerebral artery occlusion. At approximately day 30,
11
C-flumazenil (FMZ), a potential positron emission tomography marker of selective neuronal loss, and structural magnetic resonance-based infarct mapping were obtained, and the brain was perfused-fixed. Reduced FMZ binding in noninfarcted cortical middle cerebral artery areas was searched voxel-wise, and specific binding was assessed using compartmental modeling of FMZ time-activity curves.

Results—

Visual inspection revealed reduced late FMZ uptake in the affected cortical territory, extending well beyond the infarct. Accordingly, the incidence of selected voxels was greater than chance, documenting mildly but significantly reduced FMZ uptake and specific binding. Serial
15
O positron emission tomography revealed moderately severe acute ischemia followed by reperfusion. Histopathology documented only mild neuronal changes in or near the affected areas.

Conclusions—

We document moderate but definite late FMZ binding decrements in noninfarcted cortical areas in the baboon, consistent with previous rat and human studies. These were acutely characterized by moderate ischemia followed by reperfusion, consistent with neuronal damage from ischemic or reperfusion injury in the salvaged at-risk tissue. Only mild histopathological changes subtended these FMZ alterations suggesting subtle processes such as isolated dendrite or synapse loss. Whether these changes impact on clinical outcome deserves studying because they may be targeted by specific neuroprotection.
Hyperbaric Oxygen Reduces Tissue Hypoxia and Hypoxia-Inducible Factor-1α Expression in Focal Cerebral Ischemia
Authors: Sun Li , Marti Hugo H. , Veltkamp Roland
Published: February 2008

Background and Purpose—

The usefulness of hyperbaric oxygen (HBO) and normobaric hyperoxia in acute ischemic stroke is being reexplored because both improve outcome in experimental cerebral ischemia. However, even the basic mechanisms underlying oxygen therapy are poorly understood. We investigated the effect of both oxygen therapies on tissue hypoxia and on the transcription factor hypoxia-inducible factor-1α.

Methods—

Mice were subjected to filament-induced middle cerebral artery occlusion for 2 hours. Twenty-five minutes after filament introduction, mice breathed normobaric air, normobaric 100% O
2
(normobaric hyperoxia), or 100% O
2
at 3 ata (HBO) for 95 minutes. Hypoxic regions were mapped on tissue sections after preischemic infusion of the in vivo hypoxia marker EF-5. Hypoxia-inducible factor-1α protein was measured after 2-hour middle cerebral artery occlusion using immunofluorescence and immunoblotting. Vascular endothelial growth factor expression was analyzed using in situ mRNA hybridization.

Results—

Severity of ischemia did not differ among groups. HBO (35.2±10.4 mm
2
) significantly reduced the area of EF-5-stained hypoxic regions in focal cerebral ischemia compared with normobaric hyperoxia (46.4±11.2 mm
2
) and air (49.1±8 mm
2
,
P
<0.05, analysis of variance). Topographically, EF-5 fluorescence was decreased in medial striatum and in cortical ischemic border areas. Immunohistochemistry and immunoblotting revealed lower hypoxia-inducible factor-1α protein in the ischemic hemisphere of HBO-treated mice. Moreover, mRNA in situ hybridization showed lower expression of vascular endothelial growth factor in HBO and normobaric hyperoxia groups.

Conclusions—

Measurement of extrinsic and intrinsic markers of hypoxia revealed that HBO improves penumbral oxygenation in focal ischemia. Modification of the transcription factor hypoxia-inducible factor-1α and its downstream targets may be involved in effects of HBO.
Brain-Derived Neurotrophic Factor But Not Forced Arm Use Improves Long-Term Outcome After Photothrombotic Stroke and Transiently Upregulates Binding Densities of Excitatory Glutamate Receptors in the Rat Brain
Authors: Müller Harald D. , Hanumanthiah Kiran M. , Diederich Kai , Schwab Stefan , Schäbitz Wolf-Rüdiger , Sommer Clemens
Published: February 2008

Background and Purpose—

Both application of neurotrophic factors like brain-derived neurotrophic factor (BDNF) and constraint-induced movement therapy like forced arm use have been shown to potentially improve outcome after stroke. The aim of the present study was to check whether postischemic long-term outcome correlates to specific modifications in the abundance of various neurotransmitter receptors.

Methods—

Adult male Wistar rats were subjected to photothrombotic ischemia and assigned to various treatment groups (n=5 each) with end points at 3 and 6 weeks: (1) ischemic control (saline); (2) BDNF (ischemia, 20 μg BDNF); (3) forced arm use (ischemia, saline, and ipsilateral plaster cast for 5 or 14 days for the 3- and 6-week groups, respectively); and (4) combined treatment (combi; ischemia, 20 μg BDNF, forced arm use). Animals received intravenous bolus infusions of saline or BDNF 1 hour 3 and 5 days after ischemia, respectively. A group of sham rats (n=2) served as a control. A battery of behavioral tests was performed before and up to 6 weeks after ischemia. Quantitative in vitro receptor autoradiography was performed on 12-μm-thick cryostat sections using [
3
H]MK-801, [
3
H]AMPA, and [
3
H]muscimol for labeling of NMDA, AMPA, and GABA
A
receptors, respectively.

Results—

Best functional outcome was seen after BDNF treatment, whereas vice versa rats with forced arm use did worse in behavioral performance. Improved behavioral outcome was associated with increased perilesional binding densities of NMDA and AMPA receptors 3 weeks after stroke.

Conclusions—

Our findings suggest that transient enhanced neurotransmission as reflected by increased ligand binding of NMDA and AMPA receptors may participate in successful postlesional reorganization processes.
Fibrinogen γ′ in Ischemic Stroke
Authors: Cheung Elim Y.L. , de Willige Shirley Uitte , Vos Hans L. , Leebeek Frank W.G. , Dippel Diederik W.J. , Bertina Rogier M. , de Maat Moniek P.M.
Published: February 2008

Background and Purpose—

To determine the contribution of fibrinogen γ′ levels and
FGG
haplotypes to ischemic stroke.

Methods—

Associations between fibrinogen γ′ levels, fibrinogen γ′/total fibrinogen ratio, and
FGG
haplotypes with the risk of ischemic stroke were determined in 124 cases and 125 controls.

Results—

Fibrinogen γ′/total fibrinogen ratio was higher in patients than in controls during the acute phase of the stroke and lower in the convalescent phase 3 months after the stroke.
FGG
haplotype 3 (H3) was associated with a reduced risk of ischemic stroke (odds ratio 0.60; 95% CI, 0.38 to 0.94), but not with the fibrinogen γ′/total fibrinogen ratio. In contrast, FGG-H2 was associated with a decreased fibrinogen γ′/total fibrinogen ratio, but not with risk of stroke.

Conclusions—

Fibrinogen γ′/total fibrinogen ratio is associated with ischemic stroke, especially in the acute phase of the disease. In addition, FGG-H3 haplotype appears to be protective against ischemic stroke.
Reverse Regulation of Endothelial Cells and Myointimal Hyperplasia on Cell Proliferation by a Heatshock Protein-Coinducer After Hypoxia
Authors: Denes Laszlo , Bori Zoltan , Csonka Eva , Entz Laszlo , Nagy Zoltan
Published: February 2008

Background and Purpose—

Myointimal hyperplasia (MIH) cells are related to permanent upregulated proliferation as tumor-like cells. The aim of this study is to assess whether treatment of cells after hypoxia by Iroxanadine heat-shock protein (HSP-coinducer) predicts recovery through cell proliferation.

Methods—

Vascular smooth muscle cells (VSMC) and brain capillary endothelial cells (HBEC) were isolated from human origin and MIH-cells from early carotid restenosis after surgery. Cell proliferation was quantified by bromuridine (BrdU) incorporation after hypoxia/reoxygenation. HSP72 and cyclin-dependent kinase (CDKN1A) mRNA expression was assessed by reverse transcription-polymerase chain reaction (PCR) and cell cycle distribution by flow cytometry (FACS) analysis.

Results—

After hypoxia/reoxygenation, the proliferation of MIH-cells increased, whereas endothelial cells decreased (MIH: 0.266±0.016 versus 0.336±0.024;
P
<0.05; HBEC: 1.249±0.10 versus 0.878±0.11;
P
<0.05). Whereas augmented proliferation of MIH-cells was reduced (40% to 45%) by HSP-coinducer, diminished HBEC proliferation increased (46.2%). Stress-activated-protein-kinase (SAPK)p38-dependent cell cycle redistribution was generated by an increase in HSP72 and CDKN1A mRNA levels in MIH-cells.

Conclusions—

The 2 key players of early restenosis (MIH, EC) were oppositely regulated and correspondingly after treatment by HSP-coinducer reverse recovered. Drug candidate may have therapeutic potential in (re)restenosis.
Effects of Global Cerebral Ischemia in the Pregnant Rat
Authors: Spencer Sarah J. , Galic Michael A. , Tsutsui Mio , Pittman Quentin J. , Mouihate Abdeslam
Published: February 2008

Background and Purpose—

Stroke during pregnancy is an emerging concern. Although females undergo many physiological, endocrine, and neurological alterations during pregnancy, the consequences of such changes on outcome after stroke are unclear. It is predicted that increases in steroid hormones observed during pregnancy may confer protective effects against the neurological and pathological sequelae of stroke.

Methods—

We therefore investigated behavioral and histological consequences of a global cerebral ischemia (2-vessel occlusion; 2VO), and how these outcomes correlated with pregnancy-related changes in hormones in Sprague-Dawley rats.

Results—

After the 2VO, pregnant rats exhibited poorer memory in a contextual fear conditioning test of learning and memory than sham-treated controls, whereas nonpregnant rats did not. They also showed enhanced CA1 hippocampal neuronal injury. This susceptibility to damage is despite significant pregnancy-associated hypothermia and is probably not associated with alterations in 17β-estradiol or corticosterone levels.

Conclusion—

These findings are the first to show enhanced neuronal damage in pregnant animals after global cerebral ischemia. They also suggest that the mechanism may be independent of changes in estrogen, corticosterone, and body temperature.
Delayed Tolerance With Repetitive Transient Focal Ischemic Preconditioning in the Mouse
Authors: Zhang Jian , Yang Zeng-Jin , Klaus Judith A. , Koehler Raymond C. , Huang Judy
Published: February 2008

Background and Purpose—

Transient ischemic attacks have long been regarded as a risk factor for the incidence of stroke but may reduce the severity of stroke by inducing ischemic tolerance. The present objective was to develop an ischemic preconditioning (IPC) model of delayed tolerance in the mouse based on repetitive, transient middle cerebral artery occlusion (MCAO).

Methods—

Mice anesthetized with halothane or isoflurane underwent IPC, which consisted of repetitive MCAO at 45-minute intervals by the intraluminal filament technique. A 90-minute test MCAO was performed 24 to 96 hours later.

Results—

Using an IPC of 2 5-minute MCAO episodes, the reduction in infarct volume from the test MCAO was maximal with a 72-hour delay in striatum (70%) and cerebral cortex (64%) when halothane was used for surgical anesthesia. With isoflurane anesthesia, the reduction in infarct volume was less prominent in striatum (34%) and not significant in cortex (9%) despite similar levels of arterial pressure and decreases in cortical perfusion. Neuronal cell death was rare 6 days after this IPC stimulus alone with halothane or isoflurane. Increasing the severity of IPC to 3 5-minute bouts or 1 15-minute bout of MCAO in the presence of isoflurane anesthesia augmented the reduction in infarct volume in striatum and cortex, but it also augmented selective neuronal cell death in striatum after the IPC stimulus alone.

Conclusions—

These data demonstrate that a repetitive focal IPC stimulus can be titrated to induce delayed tolerance in both striatum and cortex of the mouse without inducing neuronal death by itself.
Involvement of Mitogen-Activated Protein Kinase Signaling in Growth and Rupture of Human Intracranial Aneurysms
Authors: Laaksamo Elisa , Tulamo Riikka , Baumann Marc , Dashti Reza , Hernesniemi Juha , Juvela Seppo , Niemelä Mika , Laakso Aki
Published: February 2008

Background and Purpose—

Mitogen-activated protein kinases (MAPKs) are involved in vascular wall remodeling, but their role in the pathogenesis of intracranial aneurysms (IAs) is poorly known. We investigated the expression and phosphorylation of the 3 major mitogen-activated protein kinases, c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase, in unruptured and ruptured human IAs.

Methods—

Tissue samples (n=24, 12 unruptured and 12 ruptured IAs) were obtained during microneurosurgical clipping. The localization of the proteins was studied by immunofluorescent staining, and protein levels and phosphorylation state were studied by Western blotting.

Results—

The phosphorylation of p54 JNK was increased 1.5-fold in ruptured IAs and the phospho-p54 JNK level and its phosphorylation state directly correlated with IA size. The levels of phosphorylated and total levels of p38 were associated with IA size as well. Extracellular signal-regulated kinase did not associate with IA size or rupture status. Expression of transcription factor c-Jun, a downstream target of JNK, correlated with p54 JNK level and phosphorylation state. Furthermore, the levels of matrix metalloproteinase 9, known to have a role in vessel wall degeneration, correlated with p54 JNK phosphorylation in unruptured IAs and its expression was increased 4.3-fold in ruptured IAs.

Conclusions—

Our results suggest that JNK activity and expression are involved in IA growth and possibly rupture and p38 expression in IA growth. Thus, pharmacological therapy affecting the stress-activated mitogen-activated protein kinases, JNK and p38, may enhance the repair of the IA wall in the future.
Empirical Evidence of Bias in the Design of Experimental Stroke Studies
Authors: Crossley Nicolas A. , Sena Emily , Goehler Jos , Horn Jannekke , van der Worp Bart , Bath Philip M.W. , Macleod Malcolm , Dirnagl Ulrich
Published: February 2008

Background and Purpose—

At least part of the failure in the transition from experimental to clinical studies in stroke has been attributed to the imprecision introduced by problems in the design of experimental stroke studies. Using a metaepidemiologic approach, we addressed the effect of randomization, blinding, and use of comorbid animals on the estimate of how effectively therapeutic interventions reduce infarct size.

Methods—

Electronic and manual searches were performed to identify meta-analyses that described interventions in experimental stroke. For each meta-analysis thus identified, a reanalysis was conducted to estimate the impact of various quality items on the estimate of efficacy, and these estimates were combined in a meta–meta-analysis to obtain a summary measure of the impact of the various design characteristics.

Results—

Thirteen meta-analyses that described outcomes in 15 635 animals were included. Studies that included unblinded induction of ischemia reported effect sizes 13.1% (95% CI, 26.4% to 0.2%) greater than studies that included blinding, and studies that included healthy animals instead of animals with comorbidities overstated the effect size by 11.5% (95% CI, 21.2% to 1.8%). No significant effect was found for randomization, blinded outcome assessment, or high aggregate CAMARADES quality score.

Conclusions—

We provide empirical evidence of bias in the design of studies, with studies that included unblinded induction of ischemia or healthy animals overestimating the effectiveness of the intervention. This bias could account for the failure in the transition from bench to bedside of stroke therapies.
Prevalence and Prognosis of Coexistent Asymptomatic Intracranial Stenosis
Authors: Nahab Fadi , Cotsonis George , Lynn Michael , Feldmann Edward , Chaturvedi Seemant , Hemphill J. Claude , Zweifler Richard , Johnston Karen , Bonovich David , Kasner Scott , Chimowitz Marc
Published: February 2008

Background and Purpose—

There are limited data on the prevalence and prognosis of asymptomatic intracranial stenosis (AIS).

Methods—

Baseline cerebral angiograms and MR angiograms were used to determine AIS (50% to 99%) coexistent to symptomatic intracranial stenosis for patients enrolled in the Warfarin-Aspirin Symptomatic Intracranial Disease study.

Results—

Coexisting AIS were detected in 18.9% (n=14/74) of patients undergoing 4-vessel cerebral angiography and 27.3% (n=65/238) of patients undergoing MR angiogram. During a mean follow-up period of 1.8 years, no ischemic strokes were attributable to an AIS on cerebral angiography and 5 ischemic strokes (5.9%, 95% CI: 2.1% to 12.3%) occurred in the AIS territory on MR angiogram (risk at 1 year=3.5%, 95% CI: 0.8% to 9.0%).

Conclusions—

Whereas the prevalence of coexisting AIS (50% to 99%) in patients with symptomatic stenosis is high, the risk of stroke from these asymptomatic stenoses is low.
Jesus der Jude Die jüdische Leben-Jesu-Forschung von Abraham Geiger bis Ernst Ludwig Ehrlich
Authors: Homolka Walter
Published: February 2008

The article provides an overview of Jewish Life-of-Jesus research from Abraham Geiger to Ernst Ludwig Ehrlich. Julius Wellhausen's assessment that Jesus was not Christian but Jewish encountered a Jewish community that was striving for civic equality in the course of the Enlightenment and that saw itself impaired by the idea of the ,,Christian state". The ensuing Jewish concern with the central figure of the New Testament was not of fundamental nature, but rather followed from an apologetic impulse: the wish to participate in general society without having to give up Jewish identity. Since then, many Jewish thinkers of the modern era have studied Jesus. The essay outlines the history of ,,bringing Jesus home" to Judaism, which has been observed since the nineteenth century. Jesus returns as exemplary Jew, as hortatory prophet, as revolutionary and freedom fighter, as big brother and messianic Zionist. The foremost intention though was that Jews wanted to remain Jews and nevertheless be part of Christian society. How fortunate, therefore, that Jesus was Jewish.
Monstranz – Gott zeigen Das Fronleichnamsfest aus systemtheoretischer Perspektive
Authors: Hafner Johann EV.
Published: February 2008

The Feast of Corpus Christi was only able to assert itself after it came to be connected with a procession. In this visual rite a host in a monstrance is carried through the streets. The intention is to emphasize the substantial presence of Christ in the "accidental" form of bread. In studying such rites, a scholarly approach to religion does not limit itself to popular custom or sacramental theology, but also asks about the underlying functions of the feast of Corpus Christi. The following article interprets the Corpus Christi procession as a diffusion and expansion of the believer's focused attention. This, in turn, was a reaction to the overly strong emphasis on external appearances of piety when the host was elevated. The host itself may be interpreted as the blind spot of religious observation because it functions as a visible sign of the transcendental that is not further interpreted, but is displayed in silence. It is neither negated nor affirmed, though its meaning is presumed and is operationally repeated.
Jahresringe der Religions- und Geistesgeschichte Jubiläen und Erinnerungen anläßlich des 100. Geburtstages von Hans-Joachim Schoeps, des ,,60sten" der ,,Zeitschrift für Religions- und Geistesgeschichte" und des ,,50sten" der ,,Gesellschaft für Geistesgeschichte"
Authors: Knoll Joachim H.
Published: February 2008

In the near future three anniversaries are to be celebrated: Hans-Joachim Schoeps, German-Jewish scholar and full Professor of Religious and Intellectual History, would have been 100 years old in January 2009. Jointly together with Ernst Benz, full Professor of Theology at the University of Marburg, Hans-Joachim Schoeps launched the Journal of religious and intellectual history (ZRGG), which is now entering its 60th volume. Also, the Scientific Association for religious and intellectual history (GGG), which was as well founded by Hans-Joachim Schoeps, is going to celebrate its 50th anniversary. The article depicts biographical data and scholarly highlights of Schoeps, and combines them with a view to the development of ZRGG and GGG.
Valores de los jóvenes universitarios palestinos
Authors: El-Asial Sofián
Published: February 2008

En el presente trabajo se plantea como objetivo averiguar los valores de los jóvenes universitarios palestinos. La muestra, representativa de la población palestina, ha sido de 405 sujetos. Se ha tenido en cuenta las variables sociodemográficas como el sexo y la edad (19–22 años). Se ha utilizado la Encuesta de Valores de Rokeach, que recoje valores finales e instrumentales (Rokeach, 1973); además, hemos utilizado parte del Cuestionario de Valores de la UNESCO de 1987 (cfr. Cazorla, 1988). En general, los resultados desvelan que el perfil de los valores de los jóvenes palestinos resulta estar vinculado al valor religión.
Conflicto interparental, relaciones padres-hijos e impacto emocional en los hijos
Authors: Cosgaya Leire , Nolte Marta , Martínez-Pampliega Ana , Sanz Mireia , Iraurgi Ioseba
Published: February 2008

Se analiza la relación entre el conflicto interparental, las relaciones entre padres-hijos y el impacto emocional en estos últimos. A través de un diseño transversal se ha encuestado a 655 adolescentes (374 chicas y 281 chicos). Para la valoración de las variables de interés se ha utilizado una batería de cuestionarios que comprende los siguientes: la Escala de Percepción de los Hijos del Conflicto Interparental (CPIC), el inventario para los Hijos del Comportamiento Parental (CRPBI), y la Escala de Psicopatología Infanto-juvenil (YSR). Se han utilizado correlaciones de Pearson para explorar las asociaciones entre las variables y utilizado un modelo de regresión jerárquica para determinar las variables predictivas del impacto emocional en los hijos. Se encontraron asociaciones estadísticamente significativas (p <.01) entre las variables implicadas con efectos entre valores de 0.30 y 0.46. El modelo de regresión jerárquica explicó el 33% de la varianza y comopredictores principales del estado emocional de los hijos la percepción del conflicto (correlación semiparcial rs-p = 0.33) y la hostilidad de la madre (rs-p =.19). Los resultados obtenidos permiten corroborar la hipótesis planteada en este estudio, dado que la percepción por parte de los hijos de un mayor grado de conflicto interparental y un estilo de comportamiento hostil por parte de la madre para con el hijo muestran asociación estadísticamente significativa con el malestar emocional de este último.
La universalidad del hecho cultural humano y sus consecuencias. Comentarios al debate
Authors: Bronckart Jean-Paul , Álvarez Amelia
Published: February 2008

Estos comentarios subrayan los puntos que comparten los distintos participantes en el debate: todos ellos manifiestan la misma preocupación política por la elaboración de un proyecto educativo que contemple la diversidad de las manifestaciones de la vida humana y a la vez se plantee formar personas autónomas capaces de contribuir positivamente a la dinámica evolutiva de la especie. Después, y en esta dirección, se basan en una profunda reflexión filosófica centrada en el lugar que ocupa el hecho educativo en esta misma evolución humana, como sostiene especialmente Pablo del Río. En suma, todo ello lleva por una parte a contestar radicalmente los paradigmas dominantes en la psicología (y de las ciencias humanas en general) y, por otra parte, a subrayar la necesidad de tomar en consideración dos características fundamentales de la naturaleza humana, a saber: a) que las conductas humanas se caracterizan por sus dimensiones a la par generales y particulares y b) que esas conductas y su desarrollo proceden fundamentalmente de las interacciones entre los sistemas biológico, verbal, psíquico y sociocultural. Mis críticas se refieren, en este orden, al estatuto y la causa de la diversidad de los paradigmas psicológicos; al carácter a la vez general y particular del hecho cultural y a las implicaciones de la opción histórico-cultural para un pensamiento sobre la educación-formación.
Hacia una epistemología de la complejidad. Comentarios al debate
Authors: Rodríguez-Arocho Wanda C.
Published: February 2008

En esta exposición comentamos aspectos del debate. Destacamos que todos los expositores abogaron por una epistemología de la complejidad para abordar los problemas del desarrollo y la educación. Esta epistemología reconoce una particular relación entre biología y cultura, y concede particular importancia a la actividad verbal, los textos y los discursos en la construcción de teorías de desarrollo y educación, y en sus aplicaciones prácticas. Se plantea que, aunque todos los trabajos reconocen la naturaleza ideológica, sociopolítica y ética de teoría y práctica, queda pendiente para un futuro debate elaboración de estos aspectos.
Teorías que necesitamos los investigadores y practicantes de la educación: una reflexión crítica. Contribución al debate ¿Qué teorías necesitamos en educación?
Authors: Villarini-Jusino Ángel R.
Published: February 2008

El autor argumenta en torno a la necesidad de hacer explícito el interés ético-político que orienta a toda teoría-práctica educativa, pues las teorías responden a valoraciones y propósitos humanos, a tradiciones históricas- culturales a las que pertenecemos, y a contextos socio-políticos en los que estamos situados. Como educadores comprometidos con una educación emancipadora necesitamos teorías-prácticas educativas comprensivas, abiertas, complejas, de carácter hermenéutico, ético-político, científico, crítico y con implicaciones emancipadoras. La tarea planteada a las teorías psicológicas que aspiran a servir de base a las prácticas educativas emancipadoras, es, a partir de una crítica de su situación histórica cultural, social y política y de la explicitación de la antología o cosmovisión de lo humano que le sirve de base, construir una psicología general de síntesis transdisciplinaria sobre la complejidad de la psique humana. Dentro de ese marco general, las teorías psicológicas tienen que ser elaboradas a diversos nivel de concreción hasta llegar a las más concretas, que tienen que elaborar los practicantes educativos mismos para cuidar del ser humano particular con y para el cual trabajan.
Diálogo de cercanías. Comentarios al debate
Authors: Corral Roberto
Published: February 2008

Las diferentes respuestas muestran coincidencias esenciales y la mejor de esas coincidencias es reconocer la educación como actividad fundacional del ser humano. Supone la doble responsabilidad política de asumir un modelo de sociedad y de ser humano como meta, y al mismo tiempo, formar personas con capacidad para decidir y participar, libres y autorregulados. Se siguen otras ideas acerca de las reformas educativas, el papel de maestros y estudiantes, y las críticas a las teorías psicológicas absolutas. Se insiste en la idea de la multiplicidad de culturas en la que cada individuo existe y la importancia de comprender los sistemas simbólicos de manera más amplia que el lenguaje. Existe acuerdo en que el enfoque histórico social pudiera ser una teoría de la integración.
Las teorías científicas ante los problemas formativos. Contribución al debate ¿Qué teorías necesitamos en educación?
Authors: Bronckart Jean-Paul , Álvarez Amelia
Published: February 2008

El problema de las teorías de referencia pertinentes para emprender intervenciones formativas remite al problema más general del estado actual del avance de las ciencias humanas y sociales, así como del lugar y el papel que ocupan los procesos de educación-formación en el seno de esas ciencias. Cualquier toma de postura sobre estas cuestiones reposa necesariamente en orientaciones filosóficas y epistemológicas (o al menos en preconcepciones” de carácter ontológico) relativas al lugar que ocupa lo humano en el universo, así como a las condiciones y desafíos de la formación y del desarrollo de los seres humanos.

En este artículo se comienza por plantear un anclaje filosófico centrado en el problema de la hominización, dividido a su vez en dos partes: una aproximación al estatuto del “devenir del universo” y una aproximación a las características de la “ruptura humana” en el transcurrir de ese proceso. Sobre esa base, se aborda el problema de la situación de las teorías de referencia que podrían ser requeridas desde el campo educativo, así como el de la necesaria autonomía de un “pensamiento” de la educación-formación. Finalmente, se intenta proporcionar respuestas, modestas pero comprometidas, a las preguntas de partida.
Seasonal Evolution of the Upwelling Process South of Cape Blanco*
Authors: Ramp Steven R. , Bahr Frederick L.
Published: February 2008

Bursts of upwelling-favorable winds lasting 4–20 days occur year-round south of Cape Blanco, a major headland on the Oregon coast. The ocean’s response to these events was studied using moored current, temperature, and salinity data; satellite SST data; and a few across-shelf sections near the mooring site. The mooring was located at 42°26.49′N, 124°34.47′W, 6 n mi off Gold Beach, Oregon, from May 2000 to October 2003. After the spring transition but before upwelling jet separation, equatorward wind stress produced a steady upwelling response much the same as a long, straight coast. Currents and winds had similar spectral characteristics with a peak near 15 days. After jet separation, upwelling-favorable winds forced a much more variable current consisting of a series of thin equatorward jets that evolved and moved offshore across the mooring, with shorter time scales than the wind stress forcing. During autumn, the equatorward wind stress weakened slightly and a transition period occurred, with the flow often poleward along the bottom. During winter, the water column was unstratified during poleward winds and currents with little variation in SST across the shelf. Winter upwelling restratified the water column from the bottom up by drawing cold, salty water onshore along the bottom, with little or no change in SST. This scenario was modulated by strong intraseasonal and interannual variability in the ocean and atmosphere. A wavelet transform analysis of alongshore wind stress and the first empirical orthogonal mode of the alongshore currents revealed strong energy peaks in the 30–70-day band. These signals were particularly clear in the ocean and were not coherent with the local wind stress, suggesting they were due to Kelvin waves of equatorial origin. The shift toward longer (40–45–60 days) periods from 2000 to 2003 was consistent with decreasing (warming) northern oscillation index, suggesting that the period as well as the energy of the intraseasonal waves may be important in transmitting heat poleward during warm years.
Mesoscale to Submesoscale Transition in the California Current System. Part I: Flow Structure, Eddy Flux, and Observational Tests
Authors: Capet X. , McWilliams J. C. , Molemaker M. J. , Shchepetkin A. F.
Published: February 2008

In computational simulations of an idealized subtropical eastern boundary upwelling current system, similar to the California Current, a submesoscale transition occurs in the eddy variability as the horizontal grid scale is reduced to O(1) km. This first paper (in a series of three) describes the transition in terms of the emergent flow structure and the associated time-averaged eddy fluxes. In addition to the mesoscale eddies that arise from a primary instability of the alongshore, wind-driven currents, significant energy is transferred into submesoscale fronts and vortices in the upper ocean. The submesoscale arises through surface frontogenesis growing off upwelled cold filaments that are pulled offshore and strained in between the mesoscale eddy centers. In turn, some submesoscale fronts become unstable and develop submesoscale meanders and fragment into roll-up vortices. Associated with this phenomenon are a large vertical vorticity and Rossby number, a large vertical velocity, relatively flat horizontal spectra (contrary to the prevailing view of mesoscale dynamics), a large vertical buoyancy flux acting to restratify the upper ocean, a submesoscale energy conversion from potential to kinetic, a significant spatial and temporal intermittency in the upper ocean, and material exchanges between the surface boundary layer and pycnocline. Comparison with available observations indicates that submesoscale fronts and instabilities occur widely in the upper ocean, with characteristics similar to the simulations.
Interannual Variability in the Pathways of the North Atlantic Current over the Mid-Atlantic Ridge and the Impact of Topography
Authors: Bower Amy S. , von Appen Wilken-Jon
Published: February 2008

Recent studies have indicated that the North Atlantic Ocean subpolar gyre circulation undergoes significant interannual-to-decadal changes in response to variability in atmospheric forcing. There are also observations, however, suggesting that the southern limb of the subpolar gyre, namely, the eastward-flowing North Atlantic Current (NAC), may be quasi-locked to particular latitudes in the central North Atlantic by fracture zones (gaps) in the Mid-Atlantic Ridge. This could constrain the current’s ability to respond to variability in forcing. In the present study, subsurface float trajectories at 100–1000 m collected during 1997–99 and satellite-derived surface geostrophic velocities from 1992 to 2006 are used to provide an improved description of the detailed pathways of the NAC over the ridge and their relationship to bathymetry. Both the float and satellite observations indicate that in 1997–99, the northern branch of the NAC was split into two branches as it crossed the ridge, one quasi-locked to the Charlie–Gibbs Fracture Zone (CGFZ; 52°–53°N) and the other to the Faraday Fracture Zone (50°–51°N). The longer satellite time series shows, however, that this pattern did not persist outside the float sampling period and that other branching modes persisted for one or more years, including an approximately 12-month time period in 2002–03 when the strongest eastward flow over the ridge was at ∼49°N. Schott et al. showed how northward excursions of the NAC can temporarily block the westward flow of the Iceland–Scotland Overflow Water through the CGFZ. From the 13-yr time series of surface geostrophic velocity, it is estimated that such blocking may occur on average 6% of the time, although estimates for any given 12-month period range from 0% to 35%.