bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional Desensitization of β-Adrenergic Receptor Signaling in Swine With Chronic Hibernating Myocardium
Authors: Iyer Vijay S. , Canty John M.
Published: September 2005

Contractile reserve during submaximal β-adrenergic stimulation is attenuated in patients and swine with hibernating myocardium. We tested the hypothesis that this arises as a regional adaptive response in β-adrenergic adenylyl cyclase coupling. Pigs (n=8) were studied 3 months after instrumentation with a left anterior descending artery (LAD) stenosis when flow (LAD, 0.7±0.2 versus 1.2±0.1 mL/min per gram in normal remote;
P
<0.05) and wall thickening (LAD, 5.5±3.2% versus 40.0±5.5% in remote;
P
<0.05) were reduced in the absence of infarction. Whereas basal cAMP production was normal (LAD, 87±18 versus 91±19 pmol/mg per minute;
P
=NS), responses to isoproterenol were blunted (LAD, 83±6 versus 146±25 pmol/mg per minute in remote;
P
<0.05). β-receptor density and subtype were unchanged, but there was a reduction in the number of high-affinity binding sites (LAD, 40±4% versus 53±7% in normal remote;
P
<0.05). The Giα
2
/Gsα ratio increased (LAD, 1.8±0.3 versus 0.99±0.3 in remote myocardium;
P
<0.05), although GppNHp-stimulated cAMP production was equivocally reduced. Forskolin responses were unchanged and similar to shams. These data indicate regional attenuation of β-receptor adenylyl cyclase signaling in hibernating myocardium. This blunts the local contractile response to β-adrenergic stimulation and may serve to protect against a myocardial supply/demand imbalance when external determinants of myocardial workload increase during sympathetic activation.
Liver X Receptor Activation Controls Intracellular Cholesterol Trafficking and Esterification in Human Macrophages
Authors: Rigamonti E. , Helin L. , Lestavel S. , Mutka A.L. , Lepore M. , Fontaine C. , Bouhlel M.A. , Bultel S. , Fruchart J.C. , Ikonen E. , Clavey V. , Staels B. , Chinetti-Gbaguidi G.
Published: September 2005

Liver X receptors (LXRs) are nuclear receptors that regulate macrophage cholesterol efflux by inducing ATP-binding cassette transporter A1 (ABCA1) and ABCG1/ABCG4 gene expression. The Niemann-Pick C (NPC) proteins NPC1 and NPC2 are located in the late endosome, where they control cholesterol trafficking to the plasma membrane. The mobilization of cholesterol from intracellular pools to the plasma membrane is a determinant governing its availability for efflux to extracellular acceptors. Here we investigated the influence of LXR activation on intracellular cholesterol trafficking in primary human macrophages. Synthetic LXR activators increase the amount of free cholesterol in the plasma membrane by inducing NPC1 and NPC2 gene expression. Moreover, ABCA1-dependent cholesterol efflux induced by LXR activators was drastically decreased in the presence of progesterone, which blocks postlysosomal cholesterol trafficking, and reduced when NPC1 and NPC2 mRNA expression was depleted using small interfering RNA. The stimulation of cholesterol mobilization to the plasma membrane by LXRs led to a decrease in cholesteryl ester formation and Acyl–coenzyme A cholesterol acyltransferase-1 activity. These data indicate that LXR activation enhances cholesterol trafficking to the plasma membrane, where it becomes available for efflux, at the expense of esterification, thus contributing to the overall effects of LXR agonists in the control of macrophage cholesterol homeostasis.
Glycogen Synthase Kinase 3β Inhibits Myocardin-Dependent Transcription and Hypertrophy Induction Through Site-Specific Phosphorylation
Authors: Badorff Cornel , Seeger Florian H. , Zeiher Andreas M. , Dimmeler Stefanie
Published: September 2005

Cardiomyocyte hypertrophy is transcriptionally controlled and inhibited by glycogen synthase kinase 3β (GSK3β). Myocardin is a muscle-specific transcription factor with yet unknown relation to hypertrophy. Therefore, we investigated whether myocardin is sufficient to induce cardiomyocyte hypertrophy and whether myocardin is regulated by GSK3β through site-specific phosphorylation. Adenoviral myocardin overexpression induced cardiomyocyte hypertrophy in neonatal rat cardiomyocytes, with increased cell size, total protein amount, and transcription of atrial natriuretic factor (ANF). In vitro and in vivo (HEK 293 cells) kinase assays with synthetic peptides and full-length myocardin demonstrated that myocardin was a “primed” GSK3β substrate, with serines 455 to 467 and 624 to 636 being the major GSK3β phosphorylation sites. Myocardin-induced ANF transcription and increase in total protein amount were enhanced by GSK3β blockade (10 mmol/L LiCl), indicating that GSK3β inhibits myocardin. A GSK3β phosphorylation-resistant myocardin mutant (8xA) activated ANF transcription twice as potently as wildtype myocardin under basal conditions with GSK3β being active. Conversely, a GSK3β phospho-mimetic myocardin mutant (8xD) was transcriptionally repressed after GSK3β blockade, indicating that GSK3β phosphorylation at the sites identified inhibits myocardin transcriptional activity. GAL4-myocardin fusion constructs demonstrated that GSK3β phosphorylation reduced the intrinsic myocardin transcriptional activity. A cell-permeable (Antennapedia protein transduction tag) peptide containing the mapped myocardin GSK3β motifs 624 to 636 induced hypertrophy of cultured cardiomyocytes, suggesting that the peptide acted as substrate-based GSK3β inhibitor in cardiomyocytes. Therefore, we conclude that the GSK3β–myocardin interaction constitutes a novel molecular control of cardiomyocyte hypertrophy. Phosphorylation by GSK3β comprises a novel post-transcriptional regulatory mechanism of myocardin.
Transcranial Ultrasound Brain Perfusion Assessment With a Contrast Agent-Specific Imaging Mode
Authors: Hölscher Thilo , Wilkening Wilko , Draganski Bogdan , Meves Saskia H. , Eyding Jens , Voit Heinz , Bogdahn Ulrich , Przuntek Horst , Postert Thomas
Published: September 2005

Background and Purpose—The purpose of this study was to assess brain perfusion with an ultrasound contrast-specific imaging mode and to prove if the results are comparable between 2 centers using a standardized study protocol.

Methods—A total of 32 individuals without known cerebrovascular disease were included in the study. Perfusion studies were performed ipsilaterally in an axial diencephalic plane after intravenous administration of 0.75 mL of Optison. Offline time intensity curves (TIC) were generated in different anatomic regions. Both centers used identical study protocols, ultrasound machines, and contrast agent.

Results—In both centers, the comparison of the parameter time to peak intensity (TPI) revealed significantly shorter TPIs in the main vessel structures compared with any parenchymal region of interest (ROI), whereas no significant differences were seen between the parenchymal ROIs. The parameter peak intensity (PI) varied widely interindividually in both centers, whereas theinter-ROI comparison revealed statistical significance (P<0.05) in most of the cases according to the following pattern: (1) lentiforme nucleus > thalamus and white matter region, (2) thalamus > white matter region, and (3) main vessel > any parenchymal structure. Similar results were achieved in both centers independently.

Conclusion—The study demonstrates that brain perfusion assessment with an ultrasound contrast-specific imaging mode is comparable between different centers using the same study protocol.
Role of Adenosine and Nitric Oxide on the Mechanisms of Action of Dipyridamole
Authors: Gamboa Alfredo , Abraham Robert , Diedrich Andre , Shibao Cyndya , Paranjape Sachin Y. , Farley Ginnie , Biaggioni Italo
Published: September 2005

Background and Purpose—

The combination of dipyridamole and aspirin has been shown to be more effective than aspirin alone in the secondary prevention of stroke. Dipyridamole may act by inhibiting adenosine uptake, thus potentiating its actions. Dipyridamole also inhibits cGMP-specific phosphodiesterases (PDE) and, through this mechanism, could potentiate cGMP-mediated actions of nitric oxide.

Methods—

To define the mechanism of action of dipyridamole, we studied the local vascular effects of adenosine, acetylcholine (NO-mediated dilation), and nitroprusside (cGMP-mediated dilation) in a double-blind study after treatment with dipyridamole/aspirin (200 mg dipyridamole/25 mg aspirin twice a day) or aspirin control for 7 days in 6 normal volunteers. Vasodilators were administered into the brachial artery in the nondominant arm in random order and forearm blood flow (FBF) was measured by venous occlusion plethysmography.

Results—

Adenosine at a dosage of 125 μg/min increased FBF from 4.6±0.9 to 29.4±5.3 (539% increase) with dipyridamole/aspirin and from 3.9±0.8 to 12±2.5 mL/100 mL forearm/min (208% increase) with aspirin alone (
P
=0.007). In contrast, dipyridamole/aspirin did not alter the response to acetylcholine or to nitroprusside. The magnitude of adenosine-induced vasodilation correlated with plasma dipyridamole concentrations (
r
2
=0.6); no correlation was observed with acetylcholine- or nitroprusside-induced vasodilation. Similar potentiation of adenosine, but not acetylcholine or nitroprusside, was observed in 7 additional subjects when adenosine, acetylcholine, and nitroprusside were given in random order before and 2 hours after a single dose of dipyridamole/aspirin.

Conclusion—

The effects of dipyridamole on resistance vessels are preferentially explained by potentiation of adenosine mechanisms rather than potentiation of nitric oxide or other cGMP-mediated actions.
Small Vessel Disease and General Cognitive Function in Nondisabled Elderly
Authors: van der Flier Wiesje M. , van Straaten Elizabeth C.W. , Barkhof Frederik , Verdelho Ana , Madureira Sofia , Pantoni Leonardo , Inzitari Domenico , Erkinjuntti Timo , Crisby Militta , Waldemar Gunhild , Schmidt Reinhold , Fazekas Franz , Scheltens Philip
Published: September 2005

Background and Purpose—

On cerebral magnetic resonance imaging (MRI), white matter hyperintensities (WMH) and lacunes are generally viewed as evidence of small vessel disease. The clinical significance of small vessel disease in terms of global cognitive function has as yet not been completely clarified. We investigated the independent contribution of WMH and lacunes to general cognitive function in a group of independently living elderly with varying degrees of small vessel disease.

Methods—

Data were drawn from the multicenter, multinational Leukokraurosis and Disability (LADIS) study. There were 633 independently living participants. General cognitive function was assessed using the Mini Mental State Examination (MMSE) and the modified Alzheimer Disease Assessment Scale (ADAS). On MRI, WMH was rated as mild, moderate, or severe. Lacunes were rated as none, few (1 to 3), or many (4 or more).

Results—

In the basic analysis, increasing severity of both WMH and lacunes was related to deteriorating score on the MMSE and ADAS. When WMH and lacunes were entered simultaneously, both MRI measures remained significantly associated with MMSE score. Increasing severity of WMH remained associated with ADAS score, whereas the association with lacunes became less prominent. These associations were independent of other risk factors for dementia, like education, depression, vascular risk factors, or stroke.

Conclusion—

We found WMH and lacunes to be independently associated with general cognitive function in a sample of independently living elderly. These results highlight the fact that WMH and lacunes should both be evaluated when assessing small vessel disease in relation to cognitive function.
Chronic Mild Reduction of Cerebral Perfusion Pressure Induces Ischemic Tolerance in Focal Cerebral Ischemia
Authors: Kitagawa Kazuo , Yagita Yoshiki , Sasaki Tsutomu , Sugiura Shiro , Omura-Matsuoka Emi , Mabuchi Takuma , Matsushita Kohji , Hori Masatsugu
Published: September 2005

Background and Purpose—

Neurons acquire tolerance to ischemic stress when preconditioning ischemia occurs a few days beforehand. We focused on collateral development after mild reduction of perfusion pressure to find an endogenous response of the vascular system that contributes to development of ischemic tolerance.

Methods—

After attachment of a probe, the left common carotid artery (CCA) of C57BL/6 mice was occluded. The left middle cerebral artery (MCA) was subsequently occluded permanently on days 0, 1, 4, 14, and 28 (n=8 each). The change in cortical perfusion during MCA occlusion was recorded. A sham group of mice received only exposure of the CCA and MCA occlusion 14 days later. In apoE-knockout mice, the MCA was occluded 14 days after CCA occlusion or sham surgery. Infarct size and neurologic deficit were determined 4 days after MCA occlusion.

Results—

Mice that had 45% to 65% of baseline perfusion after CCA occlusion were used. Cortical perfusion after MCA occlusion was significantly preserved in day 14 (47±16%) and day 28 (46±7%) groups compared with day 0 (28±8%), day 1 (33±19%), day 4 (29±16%), and sham groups (32±9%). Infarct size and neurologic deficits were also attenuated in day 14 and day 28 groups compared with other groups. In apoE-knockout mice, there was no significant difference in perfusion, neurologic deficits, or infarction size between groups with and without CCA occlusion.

Conclusion—

Chronic mild reduction of perfusion pressure resulted in preservation of cortical perfusion and attenuation of infarct size after MCA occlusion. These responses of collaterals were impaired in apoE-knockout mice.
Inhibition of Rho Kinase (ROCK) Leads to Increased Cerebral Blood Flow and Stroke Protection
Authors: Rikitake Yoshiyuki , Kim Hyung-Hwan , Huang Zhihong , Seto Minoru , Yano Kazuo , Asano Toshio , Moskowitz Michael A. , Liao James K.
Published: September 2005

Background and Purpose—

Endothelium-derived nitric oxide (NO) plays a pivotal role in vascular protection. The Rho kinase (ROCK) inhibitor, hydroxyfasudil, prevents the downregulation of endothelial NO synthase (eNOS) under hypoxic conditions. However, it is unknown whether inhibition of ROCK can attenuate ischemia-induced endothelial dysfunction and tissue damage in vivo.

Methods—

Human vascular endothelial cells were treated with increasing concentrations of hydroxyfasudil (0.1 to 100 μmol/L) and eNOS expression and activity were measured. To determine the physiological relevance of eNOS regulation by ROCK, we administered fasudil, which is metabolized to hydroxyfasudil in vivo, to mice for 2 days before subjecting them to middle cerebral artery occlusion. Cerebral blood flow, cerebral infarct size, and neurologic deficit were measured.

Results—

In a concentration-dependent manner, hydroxyfasudil increased eNOS mRNA and protein expression, resulting in a 1.9- and 1.6-fold increase, respectively, at 10 μmol/L (
P
<0.05 for both). This correlated with a 1.5- and 2.3-fold increase in eNOS activity and NO production, respectively (
P
<0.05 for both). Fasudil increased cerebral blood flow to both ischemic and nonischemic brain areas, reduced cerebral infarct size by 33%, and improved neurologic deficit score by 37% (
P
<0.05). This correlated with inhibition of brain and vascular ROCK activity and increased eNOS expression and activity. Another ROCK inhibitor, Y-27632, also showed similar effects. The neuroprotective effects of fasudil were absent in eNOS-deficient mice.

Conclusions—

These findings indicate that the neuroprotective effect of ROCK inhibition is mediated by endothelium-derived NO and suggest that ROCK may be an important therapeutic target for ischemic stroke.
Plasminogen Activators Contribute to Impairment of Hypercapnic and Hypotensive Cerebrovasodilation After Cerebral Hypoxia/Ischemia in the Newborn Pig
Authors: Armstead William M. , Cines Douglas B. , Higazi Abd Al-Roof
Published: September 2005

Background and Purpose—

Babies are frequently exposed to hypoxia and ischemia during the perinatal period as a result of stroke or problems with delivery or respiratory management post delivery. The only U.S. Food and Drug Administration-approved treatment for acute stroke is the administration of tPA. Nonetheless, basic science studies indicate that tPA exhibits both beneficial and deleterious effects on central nervous system function. Cerebral hypoxia/ischemia (H/I) impairs dilation to hypercapnia and hypotension in the newborn pig. We investigated the role of exogenous and endogenous plasminogen activators (PA) in piglet hypercapnic and hypotensive dilator impairment after H/I.

Methods—

Responses to dilator stimuli were measured in chloralose-anesthetized piglets equipped with a closed cranial window before and after hypoxia (P
o
2
35 mm Hg) and subsequent global cerebral ischemia. Data (n=6) were analyzed by repeated-measures analysis of variance.

Results—

Hypercapnic (P
co
2
75 mm Hg) and hypotensive (mean arterial blood pressure decreased by 45%) pial artery dilation (PAD) was blunted after H/I and reversed to vasoconstriction in animals pretreated with tPA or uPA (10
−7
mol/L; 26±2, 11±1, and −4±1% for hypercapnia before, after H/I, and after H/I with tPA). In animals pretreated with EEIIMD (10
−7
mol/L), a peptide that binds uPA and tPA but does not affect proteolysis or soluble uPA receptor (suPAR, 10
−7
mol/L), which binds but does not affect the proteolytic activity of uPA. PAD induced by hypercapnia and hypotension was attenuated to a lesser extent (25±2 and 17±1% for hypercapnic PAD before and after H/I in EEIIMD-pretreated animals and 21±1 and 18±2% in suPAR-pretreated animals).

Conclusions—

These data show that exogenous PA administration potentiates the impairment of hypercapnic and hypotensive PAD that occurs after H/I. Inhibition of endogenous PA may ameliorate the impairment of PAD induced by hypercapnia and hypotension PAD that develops after hypoxic central nervous system injury of diverse etiologies.
Perindopril-Based Blood Pressure–Lowering Reduces Major Vascular Events in Patients With Atrial Fibrillation and Prior Stroke or Transient Ischemic Attack
Authors: Arima Hisatomi , Hart Robert G. , Colman Sam , Chalmers John , Anderson Craig , Rodgers Anthony , Woodward Mark , MacMahon Stephen , Neal Bruce
Published: September 2005

Background and Purpose—

Patients with atrial fibrillation have a high risk of stroke and other vascular events even if anticoagulated. The primary objective here is to determine whether routine blood pressure–lowering provides additional protection for this high-risk patient group.

Methods—

This study was a subsidiary analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS)—a randomized, placebo-controlled trial that established the beneficial effects of blood pressure–lowering in a heterogeneous group of patients with cerebrovascular disease. A total of 6105 patients were randomly assigned to either active treatment (2 to 4 mg perindopril for all participants plus 2.0 to 2.5 mg indapamide for those without an indication for or a contraindication to a diuretic) or matching placebo(s). Outcomes are total major vascular events, cause-specific vascular outcomes, and death from any cause.

Results—

There were 476 patients with atrial fibrillation at baseline, of whom 51% were taking anticoagulants. In these patients, active treatment lowered mean blood pressure by 7.3/3.4 mm Hg and was associated with a 38% (95% confidence interval [CI], 6 to 59) reduction in major vascular events and 34% (95% CI, −13 to 61) reduction in stroke. The benefits of blood pressure–lowering in patients with atrial fibrillation were achieved irrespective of the use of anticoagulant therapy (
P
homogeneity=0.8) or the presence of hypertension (
P
homogeneity=0.4).

Conclusions—

For most patients with atrial fibrillation, routine blood pressure–lowering is likely to provide protection against major vascular events additional to that conferred by anticoagulation.
Long-Term Hemorrhage Risk in Children Versus Adults With Brain Arteriovenous Malformations
Authors: Fullerton Heather J. , Achrol Achal S. , Johnston S. Claiborne , McCulloch Charles E. , Higashida Randall T. , Lawton Michael T. , Sidney Stephen , Young William L.
Published: September 2005

Background and Purpose—

Children with brain arteriovenous malformations (BAVMs) are said to be at higher risk for intracranial hemorrhage (ICH) than adults. Although this notion affects treatment decisions, the evidence to support this claim is limited.

Methods—

To compare the risk of ICH in children versus adults with BAVM, we studied all cases of BAVM evaluated at the University of California, San Francisco (January 2000 to December 2004; n=400) and Kaiser Permanente Northern California (January 1993 to December 2004; n=819). In Kaplan–Meier survival analyses, the index date was the date of initial BAVM detection; cases were censored at time of subsequent ICH (the primary outcome, defined as ICH after initial presentation), first BAVM treatment, or loss to follow-up. Cox proportional hazards models included childhood presentation (<20 years old), hemorrhagic presentation, and other potential confounders.

Results—

Our study included 996 person-years of follow-up in the childhood presentation group and 3260 in the adult presentation group. In the unadjusted survival analysis, the subsequent ICH rates were similar for the 2 age groups (average annual rate 2.0% for children; 2.2% for adults;
P
=0.82 by log-rank test). BAVMs in childhood were more likely to present initially with ICH (
P
<0.001). After adjustment for presentation in the multivariate model, subsequent ICH rates were lower in children (hazard ratio, 0.10; 95% CI, 0.01 to 0.86;
P
=0.036).

Conclusions—

Children with BAVMs do not appear to be at increased risk for a subsequent ICH compared with adults, and may even be relatively protected. Confounding by hemorrhagic presentation should be considered in any study comparing BAVM hemorrhage rates in children versus adults.
Intravenous Tirofiban With Intra-Arterial Urokinase and Mechanical Thrombolysis in Stroke
Authors: Mangiafico Salvatore , Cellerini Martino , Nencini Patrizia , Gensini Gianfranco , Inzitari Domenico
Published: September 2005

Background and Purpose—

To evaluate preliminarily efficacy and safety of intravenous tirofiban combined with mechanical clot disruption and urokinase in patients with stroke attributable to major cerebral artery occlusion.

Methods—

Eleven consecutive patients with stroke attributable to acute occlusion of a major cerebral artery were treated with an intravenous bolus injection of the platelet glycoprotein IIb/IIIa antagonist tirofiban combined with heparin and by endovascular procedures including mechanical thrombolysis and locally delivered urokinase. Of the 11 cases, 9 involved angioplasty and 2 only microcatheter and microguidewire manipulation.

Results—

There were 7 patients with internal carotid or middle cerebral artery occlusion treated within 6 hours and 4 patients with basilar artery occlusion treated within 12 hours of symptom onset. Median National Institutes of Health Stroke Scale (NIHSS) score on admission was 20. After the interventional procedure, vessel recanalization was partial (thrombolysis in myocardial infarction grade flow 2 [TIMI 2]) in 7 patients and absent or insufficient in 4 patients. Twenty-four hours after the procedure, all the patients but 1 improved substantially, and on control angiography, the occluded vessel was totally patent (TIMI 3) in 10 of the 11 patients. One patient with partial recanalization did not improve and died 3 months later from pulmonary embolism. Neither a symptomatic intracerebral hemorrhage nor systemic bleedings requiring blood transfusion occurred in any patient. At discharge, median NIHSS score was 2. The 3-month outcome was excellent in 8 patients (modified Rankin Scale [mRS] 0 to 1), good in 2 patients (mRS 2), and poor in 1 patient (mRS 6).

Conclusions—

The combination of intravenous tirofiban with intra-arterial mechanical clot disruption and urokinase may be successful in reopening an occluded major cerebral vessel without increasing the hemorrhagic risk and with good functional outcome. This strategy cannot be recommended as the systematic treatment of stroke attributable to major cerebral artery occlusion until tested in a controlled study design.
Inhibition of the Cerebral Ischemic Injury by Ethyl Pyruvate With a Wide Therapeutic Window
Authors: Yu Young-Mi , Kim Jung-Bin , Lee Kang-Woo , Yun Kim Seong , Han Pyung-Lim , Lee Ja-Kyeong
Published: September 2005

Background and Purpose—

Ethyl pyruvate (EP) is a pyruvate derivative that has been reported recently to prevent lethality in mice with established lethal sepsis and systemic inflammation. In this study, we examined the neuroprotective effect of EP in a rat cerebral ischemia model of middle cerebral artery occlusion (MCAO).

Methods—

Male Sprague-Dawley rats were subjected to 1 hour of MCAO, and EP was administered at various time points before or after MCAO. The changes in the brain infarction, neurological deficits, microglia activation, and proinflammatory cytokine expression were evaluated. BV2 microglial cells were also used to access the anti-inflammatory effect of EP.

Results—

The administration of EP intraperitoneally at 30 minutes before or at 4 or 12 hours after MCAO reduced the infarct volume to 10.3±3.4% (n=6;
P
<0.05), 21.5±2.7% (n=6;
P
<0.05), and 44.3±4.0% (n=6;
P
<0.05), respectively, of that of the control group. The significant reduction in infarct volume was accompanied by the suppression of the clinical manifestations associated with cerebral ischemia, including motor impairment and neurological deficits, microglial activation, and proinflammatory cytokine expression. The neuroprotective effect of EP was yet evident when it was administered as late as 24 hours after MCAO/reperfusion (76.5±4.70%; n=6;
P
<0.05). EP suppressed lipopolysaccharide induced activation of BV2 cells, as was evidenced by a reduction in NO release and the accompanying induction of proinflammatory cytokines.

Conclusions—

These results suggest that EP affords the strong protection of the delayed cerebral ischemic injury with a wide therapeutic window.
Effect on Survival and Hospitalization of Initiating Treatment for Chronic Heart Failure With Bisoprolol Followed by Enalapril, as Compared With the Opposite Sequence
Authors: Willenheimer Ronnie , van Veldhuisen Dirk J. , Silke Bernard , Erdmann Erland , Follath Ferenc , Krum Henry , Ponikowski Piotr , Skene Allan , van de Ven Louis , Verkenne Patricia , Lechat Philippe
Published: September 2005

Background—

In patients with chronic heart failure (CHF), a β-blocker is generally added to a regimen containing an angiotensin-converting-enzyme (ACE) inhibitor. It is unknown whether β-blockade as initial therapy may be as useful.

Methods and Results—

We randomized 1010 patients with mild to moderate CHF and left ventricular ejection fraction ≤35%, who were not receiving ACE inhibitor, β-blocker, or angiotensin receptor blocker therapy, to open-label monotherapy with either bisoprolol (target dose 10 mg QD; n=505) or enalapril (target dose 10 mg BID; n=505) for 6 months, followed by their combination for 6 to 24 months. The 2 strategies were blindly compared with regard to the combined primary end point of all-cause mortality or hospitalization and with regard to each of these end point components individually. Bisoprolol-first treatment was noninferior to enalapril-first treatment if the upper limit of the 95% confidence interval (CI) for the absolute between-group difference was <5%, corresponding to a hazard ratio (HR) of 1.17. In the intention-to-treat sample, the primary end point occurred in 178 patients allocated to bisoprolol-first treatment versus 186 allocated to enalapril-first treatment (absolute difference −1.6%, 95% CI −7.6 to 4.4%, HR 0.94; 95% CI 0.77 to 1.16). In the per-protocol sample, 163 patients allocated to bisoprolol-first treatment had a primary end point, versus 165 allocated to enalapril-first treatment (absolute difference −0.7%, 95% CI −6.6 to 5.1%, HR 0.97; 95% CI 0.78 to 1.21). With bisoprolol-first treatment, 65 patients died, versus 73 with enalapril-first treatment (HR 0.88; 95% CI 0.63 to 1.22), and 151 versus 157 patients were hospitalized (HR 0.95; 95% CI 0.76 to 1.19).

Conclusion—

Although noninferiority of bisoprolol-first versus enalapril-first treatment was not proven in the per-protocol analysis, our results indicate that it may be as safe and efficacious to initiate treatment for CHF with bisoprolol as with enalapril.
Information and Expression in a Digital Age
Authors: Shah Dhavan V. , Cho Jaeho , Eveland William P. , Kwak Nojin
Published: September 2005

This article examines the role of the Internet as a source of political information and a sphere for public expression. Informational media use, whether traditional news sources or online public affairs content, is expected to foster interpersonal political discussion and online civic messaging, contributing to increased civic participation. Using two-wave national panel survey data, three types of synchronous structural equation models are tested: cross sectional (relating individual differences), fixed effects (relating intraindividual change), and auto regressive (relating aggregate change). All models reveal that online media complement traditional media to foster political discussion and civic messaging. These two forms of political expression, in turn, influence civic participation. Other variable orderings are tested to compare the theorized model to alternative causal specifications. Results reveal that the model produces the best fit, empirically and theoretically, with the influence of the Internet, rivaling the mobilizing power of traditional modes of information and expression.
When Placebic Information Differs From Real Information
Authors: Lee Eun-Ju
Published: September 2005

The present experiments investigated how individuals’ cognitive thinking styles and the influence agent’s sex would affect the extent to which people mindfully respond to informational social influence. In Study 1, participants played a trivia game with an ostensible partner via computer and were presented with either real information that provided a rationale for the partner’s choice or placebic information that merely restated accompanying self-confidence ratings in verbal format. As predicted, real information was more likely than was placebic information to elicit conformity (a) among high compared to low rationals, (b) when the partner expressed the highest ambiguity (50% confident), and (c) when a female compared to a male character represented the partner, albeit only among men. By employing more direct measures of information processing, reaction time and perceived validity of the partner’s claims, Study 2 confirmed that greater acceptance of real rather than placebic information stemmed from more effortful message decoding.
Information Exchange and Induced Cooperation in Group Decision Support Systems
Authors: Barkhi Reza
Published: September 2005

Groups are becoming increasingly important in organizations, and they use electronic groupware to facilitate communication and workflow. The author uses a 2 x 2 laboratory experiment with 96 participants to evaluate the interaction between communication channel and incentive structure when groups have to solve a mixed-motive task. The communication channel variable has two values: face-to-face (FTF) communication and computer-mediated communication (CMC). Also, the incentive structure has two values: group-based and individual-based values. This article compares the performance and information exchange truthfulness of groups under these different experimental conditions. The author utilizes a game theory perspective to study the behavior of members in these groups. The results indicate that communication channel and incentive structure mitigate strategies that lead to decision choices and information exchange truthfulness among members in a group.
From Nü Guo to Nü’er Guo
Authors: Walsh Eileen Rose
Published: September 2005

Tourism at Lugu Lake exploded in the 1990s, drawing on government representations of the Mosuo as “matriarchal” and as engaging in traditional sexual relations (zouhun) outside of marriage. The village of Luoshui is the primary tourist destination; its economy is almost completely driven by tourism. In this article, the author discusses state policy and scholarly representations of the Mosuo, tourist representations that developed from them, and the interactions and responses around ethnicity at Luoshui. Locals daily engage with the commodification of their culture and must continually negotiate tourists’ contradictory desires. The author argues that locals address these contradictions in part through performing both “front” and “backstages.” She interrogates the notion of an “authentic” Mosuo identity while describing how tourism has reified culture as a gendered consumable and has sexualized Mosuo culture in tourist areas.
Realpolitik Nationalism
Authors: Guang Lei
Published: September 2005

Conventional understandings of Chinese nationalism often portray it as anti-Western, focusing on Chinese nationalists’ obsession with a powerful state and on their ambition to recover the glory of China’s historical empire. Such understandings clearly underlie the fear and hostility toward rising Chinese nationalism today. But this view relies too heavily on China’s conflictive relations with the West and overemphasizes the impact of China’s unique history, culture, and politics, making it hard, if not impossible, to draw on the concept of nationalism in understanding China’s relations with its non-Western neighbors. Such a perspective neglects the importance of ideas and ideals from the international system that animate Chinese nationalism. In this article, the author characterizes Chinese nationalism as fusing realpolitik ideas and ideals and a fervent quest for national identity and power. A realpolitik nationalist, as defined here, is someone who frames an external threat to China in terms not of the country’s unique culture or history but of a breach of the prevailing norms of the nation-state system, whose key dimensions include sovereignty, territoriality, and international legitimacy. Finally, the author applies this notion in examining China’s conflicts with India in 1962 and with the Southeast Asian countries involved in the dispute over the Spratly Islands.
Forgiveness and Its Associations With Prosocial Thinking, Feeling, and Doing Beyond the Relationship With the Offender
Authors: Karremans Johan C. , Van Lange Paul A. M. , Holland Rob W.
Published: September 2005

Past research has revealed that forgiveness promotes prosocial cognition, feeling, and behavior toward the offender. The present research extends this research by examining whether forgiveness may spill over beyond the relationship with the offender, promoting generalized prosocial orientation. Consistent with hypotheses, three studies revealed that forgiveness compared to unforgiveness is generally associated with higher levels of a generalized prosocial orientation, as indicated by higher levels of a we frame of mind (as indicated by a greater use of first-person plural pronouns, e.g., we, us, in a language task) and greater feelings of relatedness toward others in general. Moreover, forgiveness (vs. unforgiveness) was even associated with greater probability of donating to charity and greater willingness to engage in volunteering. Finally, the authors found that unforgiveness reduces tendencies toward generalized prosocial orientation, whereas forgiveness restores generalized prosocial orientation to baseline levels within the relationship.
Individual Differences in Motivated Social Cognition: The Case of Self-Serving Information Processing
Authors: von Hippel William , Lakin Jessica L. , Shakarchi Richard J.
Published: September 2005

Three experiments examined the hypothesis that people show consistency in motivated social cognitive processing across self-serving domains. Consistent with this hypothesis, Experiment 1 revealed that people who rated a task at which they succeeded as more important than a task at which they failed also cheated on a series of math problems, but only when they could rationalize their cheating as unintentional. Experiment 2 replicated this finding and demonstrated that a self-report measure of self-deception did not predict this rationalized cheating. Experiment 3 replicated Experiments 1 and 2 and ruled out several alternative explanations. These experiments suggest that people who show motivated processing in ego-protective domains also show motivated processing in extrinsic domains. These experiments also introduce a new measurement procedure for differentiating between intentional versus rationalized cheating.
A Meta-Analysis on the Correlation Between the Implicit Association Test and Explicit Self-Report Measures
Authors: Hofmann Wilhelm , Gawronski Bertram , Gschwendner Tobias , Le Huy , Schmitt Manfred
Published: September 2005

Theoretically, low correlations between implicit and explicit measures can be due to (a) motivational biases in explicit self reports, (b) lack of introspective access to implicitly assessed representations, (c) factors influencing the retrieval of information from memory, (d) method-related characteristics of the two measures, or (e) complete independence of the underlying constructs. The present study addressed these questions from a meta-analytic perspective, investigating the correlation between the Implicit Association Test (IAT) and explicit self-report measures. Based on a sample of 126 studies, the mean effect size was .24, with approximately half of the variability across correlations attributable to moderator variables. Correlations systematically increased as a function of (a) increasing spontaneity of self-reports and (b) increasing conceptual correspondence between measures. These results suggest that implicit and explicit measures are generally related but that higher order inferences and lack of conceptual correspondence can reduce the influence of automatic associations on explicit self-reports.
The Motivational Bases of Right-Wing Authoritarianism and Social Dominance Orientation: Relations to Values and Attitudes in the Aftermath of September 11, 2001
Authors: Cohrs J. Christopher , Moschner Barbara , Maes Jürgen , Kielmann Sven
Published: September 2005

Research suggests that different motivational dynamics underlie right-wing authoritarianism (RWA) and social dominance orientation (SDO). These differences may be framed in the theory of basic human values. RWA may trace back to conservation versus openness-to-change values, and SDO to self-enhancement versus self-transcendence values. Based on a large-scale German survey, associations of RWA and SDO with personal values and attitudes in the aftermath of September 11, 2001, were analyzed. Results indicated that RWA related more strongly than SDO to conservation values and threat-related attitudes toward Islam as an expression of the motivational goals of social control and security, whereas RWA and SDO related equally to self-enhancement versus self-transcendence values and concern for negative consequences of military action as an expression of the motivational goal of altruistic concern. Thus, the motivational bases of RWA and SDO appear to be only partly different.
Considering Multiple Criteria for Social Categorization Can Reduce Intergroup Bias
Authors: Hall Natalie R. , Crisp Richard J.
Published: September 2005

Two experiments tested the notion that considering multiple criteria for social categorization can reduce intergroup bias. In both experiments, participants were required to consider alternative ways in which people could be classified, other than an initially salient intergroup dichotomy. In Experiment 1, the authors found that generating alternative social classifications that were unrelated to an initial target dichotomy reduced intergroup bias compared to a control condition. In Experiment 2, this effect was replicated and the authors found that unrelated, but not related, categorizations were necessary to reduce bias. This article adds support to the view that increasing categorical complexity is a useful tool in bias reduction. These findings are discussed in the context of a developing model of multiple categorization effects.
What’s in a Grade? Academic Success and Political Orientation
Authors: Kemmelmeier Markus , Danielson Cherry , Basten Jay
Published: September 2005

Expanding the literature on person-environment fit, the authors argue that political orientation is an important factor in shaping academic success in college. Based on social dominance theory, it was expected that academic disciplines that are more likely to provide students with future access to social and economic power tend to favor individuals who hold attitudes that strengthen the existing societal order. In a longitudinal sample of undergraduate students at a major American university(n = 3,890), the authors demonstrated that student grades in these disciplines, but not in other disciplines, are positively related to a precollege measure of conservatism. This association between conservatism is consistent over time and subgroups, thus implicating higher education in the reproduction of social hierarchy. The discussion examines the causal processes underlying the relationship between political orientation and academic success in college.
A Time to Speak, a Time to Act
Authors: Artemeva Natasha
Published: September 2005

This article discusses a longitudinal case study of a novice engineer who has successfully challenged a workplace genre. The study shows that a combination of the novice’s family background, a university engineering communication course, and workplace experiences helped him achieve success. It also provides evidence that, even though genres may differ from workplace to workplace, experienced professionals do recognize and accept superior communication practices imported from elsewhere. Thus, best practices may be taught apart from local contexts. The case study allows technical communication instructors and researchers to refine current understanding of what mastering genres means and indicates directions for the development of new pedagogies.
From Writers to Information Coordinators
Authors: Jones Scott L.
Published: September 2005

Using a previous study at the same site for comparison, this study examines how recent adoptions of intranet and improved mail technologies have altered the collaborative practices of corporate communication writers at an insurance company. A systematic analysis of collaborative activities using a newly developed continuum shows that the writers’ jobs were significantly transformed by the company’s transition to a digital concept of writing. In particular, writers focused less on producing text and more on developing, coordinating, and structuring the newly adopted corporate intranet.
The Male Attitude Norms Inventory-II
Authors: Luyt Russell
Published: September 2005

This article describes the development of the Male Attitude Norms Inventory-II (MANI II). Empirical findings and theoretical debate contributed toward the development of a measure of South African masculinity ideology. Three hundred and thirty-nine male participants, drawn from universities across greater Cape Town, were included in the study. Exploratory factor analysis rendered a three-factor model of traditional masculinity. This accounted for 31.44 percent of total item variance. Results informed the development of a Total Scale ( α = 0.90)as well as three subscale measures (Toughness, α = 0.81; Control, α = 0.82; and Sexuality, α = 0.85). The MANI-II displayed satisfactory convergent validity with the Male Role Norms Inventory (MRNI) (r = 0.84; p < 0.001). The MANI-II and MRNI subscales were also meaningfully interrelated. The MANI-II offers a contextually sensitive and multidimensional measure of masculinities. Future research should include a representative sample, establish test-retest reliability, and further examine total and subscale construct validity.
Chaos to Control
Authors: Rogers Anna
Published: September 2005

As certainties dissolve, meanings around heterosexual relationships become increasingly puzzling. Recent changes in academic/media recognition of “what it means to be a man” exacerbate this predicament. Men’s magazines attempt to escape this disorder by offering individual men a shared sense of direction. The present study looks for evidence of this in six issues of For Him Magazine (FHM) and six issues of Loaded, using a form of qualitative research closely related to grounded theory. Along with the simultaneous construction of certainty and uncertainty around intimate relationships, the analysis reveals two themes: the “sexual mode of production” stresses the practices of management, rationalization, and science and “relationship utopia” envisages a fulfilling sex life for the reader via his accomplishment of intimacy. The study concludes that the magazines move readers from chaos to control by constructing a masculinization of intimacy, whereby intimacy is incorporated into a schema broadly consistent with traditional masculinities.
Text, Body, and Tools
Authors: Brandth Berit , Haugen Marit S.
Published: September 2005

This article explores processes by which masculinities change, using examples from the Norwegian forestry industry. Forestry has traditionally been one of the most masculine rural work activities and an arena where hegemonic rural masculinity is expressed. The study is based on mediations of masculinity in a forestry magazine covering a period of twenty years. Using text, body, and tools as an analytic scheme, pictures of temporal variations of, and relations between, “traditional” and “new” types of masculinity are described. Even though practical, physical work in the forest is a basis for rural hegemonic masculinity, other types of work with new cultural influences (organizational and expert work) lead to “dialogical” masculinities, which open up for more flexible boundaries and cultural borrowing. This might be important to secure the future viability of rural industries and communities, especially if the recruitment of women is desirable.
An Application of Fear Appeal Messages to Enhance the Benefits of a Jail Encounter Program for Youthful Offenders
Authors: Windell James O. , Allen J. Scott
Published: September 2005

Research has consistently shown that so-called scared straight types of jail encounter programs do not have positive benefits for youthful offenders. However, few if any inmate-youth encounter programs have utilized the results of fear appeals message research. Results of the present study suggest that an inmate-youth encounter program may lead to attitude change in youthful offenders if components of successful fear appeals are incorporated into the program.
Juvenile Offenders and the Death Penalty
Authors: Benekos Peter J. , Merlo Alida V.
Published: September 2005

In 2002, the U.S. Supreme Court ruled that because they are less culpable and less able to deliberate about their behaviors, the execution of mentally retarded offenders exceeded the prevailing standards of decency (Atkins v. Virginia). Based on this rationale, and with increasing concerns over wrongful convictions and the execution of innocent defendants, some questioned whether the Court’s decision could also apply to juvenile offenders. In March 2005, the majority of the justices determined that executing adolescent offenders violated the Eighth Amendment (Roper v. Simmons). This article reviews (a) recent court decisions on the death penalty, (b) citizen and student opinions on juvenile executions, and (c) comparative policies on juvenile executions. The authors also discuss the politics of the death penalty and the consequences of Roper on juvenile justice policy.