bluuebunny/crossref_metadata_2025 huggingface dataset:
Results of a Survey of Patients with Alpha-1 Antitrypsin Deficiency
Authors: Strange Charlie , Stoller James K. , Sandhaus Robert A. , Dickson Ryan , Turino Gerard
Published: September 2005

Background: α1-Antitrypsin deficiency (AATD) is an uncommon genetic disease which occurs in 1–2.5% of Americans with chronic obstructive pulmonary disease (COPD). Little is known about current demographics of AATD. Objectives: This survey study reviews the clinical characteristics of diseased individuals in North America. Methods: A survey of members from the mailing lists of US AATD patient support organizations was commissioned with duplicate persons omitted. The survey was mailed to 5,222 unique individuals with AATD. Questionnaires were returned by 1,953 individuals, including 1,810 with severe deficiency, 93 with the carrier state and 41 who were caregivers of others. Results: The majority (81%) of participants reported COPD with symptoms of asthma, chronic bronchitis, and emphysema, usually in combination. The mean age of respondents [53.1 ± 13.2 (SD) years] is older than the general US population. Lung or liver transplantation was reported by 9% of all respondents (n = 175), including 66 single lung transplants, 68 double lung transplants, and 47 liver transplants. Another 6.6% (n = 128) reported that they were currently on a transplant list. Twenty-one percent of lung transplants report continuing augmentation therapy use. Augmentation use is reported by 75% of those with obstructive lung disease. The majority of patients with liver disease also have COPD. Conclusions: AATD remains a devastating illness for many of those affected as reflected in a high incidence of transplantation for liver and lung disease.
JNK/SAPK and p38 SAPK-2 Mediate Mechanical Stretch-Induced Apoptosis via Caspase-3 and -9 in NRK-52E Renal Epithelial Cells
Authors: Nguyen Hiep T. , Hsieh Michael H. , Gaborro Anna , Tinloy Bradford , Phillips Courtney , Adam Rosalyn M.
Published: September 2005

Background/Aims: In renal epithelial cells, mechanical forces produced from urinary obstruction serve as potential mediators of apoptosis by activating specific intracellular signaling pathways. In this study, we sought to further define the role of JNK and p38 SAPK-2 pathway and caspase activation in stretch-induced apoptosis. Methods: Immortalized cell lines derived from the various components of the nephron were subjected to cyclical stretch and their differential apoptotic response was assessed. Pharmacologic inhibitors and Western blot analysis were used to assess the involvement of the MAPK pathways. Caspases’ activity was assessed with ELISA and by Western blot analysis. Results: Stretch-induced apoptosis was dependent upon the cell phenotype and the degree of stretch. In NRK-52E cells, it was mediated through both JNK and p38 SAPK-2 pathways, and inhibition of either pathway reduced the degree of stretch-induced apoptosis. Stretched cells showed increased activity of caspase-3 and -9 but not -2 or -8. Stretch-induced apoptosis was modulated by inhibition of caspase-3 and to a lesser extent by caspase-9. Conclusion: These findings suggest that stretch induces apoptosis in renal epithelial cells through the specific activation of JNK/SAPK and p38 SAPK-2 pathways and is dependent on the activation of caspase-3 and -9.
Blood Pressure, White Matter Lesions and Medial Temporal Lobe Atrophy: Closing the Gap between Vascular Pathology and Alzheimer’s Disease?
Authors: Korf Esther S.C. , Scheltens Philip , Barkhof Frederik , de Leeuw Frank-Erik
Published: September 2005

Background: Vascular factors are recognized as important risk factors for Alzheimer’s disease, although it is unknown whether these factors directly lead to the typical degenerative pathology such as medial temporal lobe atrophy. We set out to investigate the relation between blood pressure and medial temporal lobe atrophy in patients with senile and presenile Alzheimer’s disease with or without white matter lesions. Methods: We determined the relation between blood pressure and pulse pressure and medial temporal lobe atrophy on MRI in 159 patients with Alzheimer’s disease, stratified on white matter lesions and age at onset of dementia. Results: There was a linear relation between systolic blood pressure and pulse pressure (both in tertiles) and the severity of medial temporal lobe atrophy (ptrend = 0.05 and ptrend 0.03, respectively). A significant relation was found between pulse pressure [β = 0.08 (95% CI: 0.00–0.15; p = 0.05) per 10 mm Hg] and (borderline significant) systolic blood pressure [β = 0.05 (95% CI: –0.01 to 0.11; p = 0.1) per 10 mm Hg] and medial temporal lobe atrophy. White matter lesions and age-stratified analysis revealed a significant association between systolic blood pressure and pulse pressure and medial temporal lobe atrophy, only in the subsample with white matter lesions and in the subsample with a senile onset of dementia. The relations were independent of severity of dementia and diabetes mellitus. Conclusions: Systolic blood pressure and pulse pressure are associated with medial temporal lobe atrophy in Alzheimer’s disease, especially in the presence of white matter lesions and in patients with a late onset of dementia. Our finding may be another step in providing a rationale on how vascular factors could ultimately result in Alzheimer’s disease.
Positive Feedbacks of Coagulation
Authors: Jesty Jolyon , Beltrami Edward
Published: September 2005

Tissue factor (TF), the initiator of coagulation, continuously circulates in the plasma, and the clotting system “idles,” generating very low levels of active clotting enzymes, clotting products, and by-products. Given the enormous amplification potential of the clotting cascade, rigorous control is required to ensure that such low-level stimulation does not cause massive system amplification and response. We propose that among the various mechanisms of regulation, activation thresholds may play a major role. These arise when positive-feedback reactions, of which there are several in the clotting system, are regulated by inhibitors. Such thresholds act like switches, so that small stimuli and/or nonproductive local conditions will generate no response, whereas larger stimuli or the existence of local prothrombotic conditions will produce a full, explosive response. We review here the evidence for system idling, the structures of the various feedback mechanisms of clotting, the mechanisms by which they can produce threshold behavior, and the possible role of thresholds in system regulation.
Toll-Like Receptor 2 Mediates Persistent Chemokine Release by
Chlamydia pneumoniae
–Infected Vascular Smooth Muscle Cells
Authors: Yang Xin , Coriolan Daniel , Schultz Kelly , Golenbock Douglas T. , Beasley Debbie
Published: September 2005

Objective—

The intracellular bacterium
Chlamydia pneumoniae
is present in many atherosclerotic lesions, where it could promote inflammation. This study determined whether monocyte chemoattractant protein 1 (MCP-1) release is stimulated in vascular smooth muscle cells (VSMCs) that are exposed to or infected by
C pneumoniae
and whether toll-like receptor 2 (TLR2) or TLR4 mediate these effects.

Methods and Results—

TLR2 mRNA was expressed constitutively and was upregulated by
C pneumoniae
exposure in mouse aortic SMC and was inducible by
C pneumoniae
and TLR3 and TLR4 agonists in human coronary artery SMCs. Exposure to inactivated or viable extracellular
C pneumoniae
evoked a robust increase in MCP-1 release and activated nuclear factor-κB and extracellular signal–regulated kinase 1/2 in wild-type and TLR4 signaling–deficient mouse aortic SMCs but not in TLR2-deficient SMCs, probably because of TLR2-mediated recognition of a chlamydial antigen. Brief exposure to viable
C pneumoniae
led to active infection of VSMCs, shown by chlamydial protein synthesis, and caused a persistent (>48-hour) MCP-1 release that was also TLR2 dependent.

Conclusions—

The results show that VSMCs express functional TLR2 and that TLR2 mediates both a persistent activation of chemokine release in
C pneumoniae
–infected VSMCs and its acute stimulation by extracellular
C pneumoniae
. Therefore, TLR2 expressed in VSMCs may promote inflammation within the arterial wall.
The Lamina Adventitia Is the Major Site of Immune Cell Accumulation in Standard Chow-Fed Apolipoprotein E–Deficient Mice
Authors: Moos Michael P.W. , John Nicole , Gräbner Rolf , Noßmann Silke , Günther Bernd , Vollandt Rüdiger , Funk Colin D. , Kaiser Brigitte , Habenicht Andreas J.R.
Published: September 2005

Objective—

Cells of adaptive immunity have been implicated in atherogenesis. Though substantial information is available on immune cells in atherosclerotic lesions of the lamina intima, cells in the lamina adventitia have received less attention.

Methods and Results—

The composition of immune cells in the innominate artery and abdominal aorta was examined in young, adult, and old apolipoprotein (apo) E
−/−
and wild-type mice on standard mouse chow. In the innominate artery of apoE
−/−
mice, adventitial T cells increased at 32, 52, and 78 weeks exceeding those of the intima by 6-, 24-, and 85-fold. Single T cells dominated in young mice, later T/B cell clusters emerged, and lymphoid-like structures reminiscent of inflammatory follicles formed preferentially in the abdominal aorta of old mice. Follicles contained organized sets of immune response-regulating cells: Interdigitating dendritic cells, T cell effectors, proliferating B cells, and plasma cells. Adventitial T cell inflammation was associated with a marked increase in transcripts of the chemokine MIP-1α in the aorta but not in spleen or liver.

Conclusions—

Adventitial lymphocyte infiltration and formation of inflammatory follicle-like structures in the abdominal aorta of old apoE
−/−
mice point to the adventitia as a site of local adaptive immune reactions during atherogenesis in hyperlipidemic mice.
AMP-Activated Protein Kinase Activates p38 Mitogen-Activated Protein Kinase by Increasing Recruitment of p38 MAPK to TAB1 in the Ischemic Heart
Authors: Li Ji , Miller Edward J. , Ninomiya-Tsuji Jun , Russell Raymond R. , Young Lawrence H.
Published: September 2005

AMP-activated protein kinase (AMPK) promotes glucose transport, maintains ATP stores, and prevents injury and apoptosis during ischemia. AMPK has several direct molecular targets in the heart but also may interact with other stress-signaling pathways. This study examined the role of AMPK in the activation of the p38 mitogen-activated protein kinase (MAPK). In isolated heart muscles, the AMPK activator 5-aminoimidazole-4-carboxy-amide-1-β-
d
-ribofuranoside (AICAR) increased p38 MAPK activation. In AMPK-deficient mouse hearts, expressing a kinase-dead (KD) α
2
catalytic subunit, p38 MAPK activation was markedly reduced during low-flow ischemia (2.3- versus 7-fold in wild-type hearts,
P
<0.01) and was similarly reduced during severe no-flow ischemia in KD hearts (
P
<0.01 versus ischemic wild type). Knockout of the p38 MAPK upstream kinase, MAPK kinase 3 (MKK3), did not affect ischemic activation of either AMPK or p38 MAPK in transgenic mkk3
−/−
mouse hearts. Ischemia increased p38 MAPK recruitment to transforming growth factor-β-activated protein kinase 1–binding protein 1 (TAB1), a scaffold protein that promotes p38 MAPK autophosphorylation. Moreover, TAB1 was associated with the α
2
catalytic subunit of AMPK. p38 MAPK recruitment to TAB1/AMPK complexes required AMPK activation and was reduced in ischemic AMPK-deficient transgenic mouse hearts. The potential role of p38 MAPK in mediating the downstream action of AMPK to promote glucose transport was also assessed. The p38 MAPK inhibitor SB203580 partially inhibited both AICAR- and hypoxia-stimulated glucose uptake and GLUT4 translocation. Activation of p38 MAPK by anisomycin also increased glucose transport in heart muscles. Thus, AMPK has an important role in promoting p38 MAPK activation in the ischemic heart by inducing p38 MAPK autophosphorylation through interaction with the scaffold protein TAB1.
Apolipoprotein E Suppresses the Type I Inflammatory Response In Vivo
Authors: Ali Kamilah , Middleton Melissa , Puré Ellen , Rader Daniel J.
Published: September 2005

Apolipoprotein E (apoE) is synthesized in the liver and in macrophages, and it has antiatherogenic properties that are mediated, at least in part, through the regulation of plasma cholesterol homeostasis. Previous data suggest that apoE also has antiinflammatory properties that may contribute to protection against atherosclerosis independent of its role in lipid metabolism. In this study, apoE knockout and C57BL/6 mice were stimulated with low-dose lipopolysaccharide (LPS) and other Toll-like receptor (TLR) agonists. We show that apoE modulates the systemic type I inflammatory response in vivo. The proinflammatory cytokines tumor necrosis factor α, interleukin (IL)-6, IL-12, and interferon-γ were upregulated to a significantly greater extent in apoE-deficient mice than in wild-type mice at both the mRNA and protein levels following administration of LPS. In contrast, hypercholesterolemic low-density lipoprotein receptor/apobec-1 double knockout mice had a similar cytokine response as wild-type mice, eliminating hypercholesterolemia as a cause for the exaggerated cytokine response. Importantly, reconstitution of apoE expression in the liver of apoE-deficient mice normalized the LPS-induced plasma protein levels of IL-12p40. Furthermore, there was selective upregulation of plasma IL-12 in apoE knockout mice by a TLR3 agonist, poly I:C, but not by other TLR agonists, CpG oligonucleotide or
Toxoplasma gondii
antigen. This implies that apoE selectively regulates TLR4- and TLR3-mediated signaling of IL-12 production. These results indicate that apoE modulates the T helper-1–type immune response in vivo by modulating IL-12 production.
Activation of the Sphingosine Kinase–Signaling Pathway by High Glucose Mediates the Proinflammatory Phenotype of Endothelial Cells
Authors: Wang Lijun , Xing Xiao-Ping , Holmes Andrew , Wadham Carol , Gamble Jennifer R. , Vadas Mathew A. , Xia Pu
Published: September 2005

Vascular endothelial cells are key targets for hyperglycemic damage that facilitates vascular inflammation and the vasculopathy associated with diabetes mellitus. However, the mechanisms underlying this damage remain undefined. We now demonstrate that hyperglycemia induces activation of sphingosine kinase (SphK), which represents a novel signaling pathway that mediates endothelial damage under ambient high glucose conditions. SphK activity was significantly increased in aorta and heart of streptozotocin-induced diabetic rats. Interestingly, this increase in SphK activity was prevented by insulin treatment, which achieved euglycemia in the diabetic animals. Hyperglycemia-induced increase in SphK activity was also evident in endothelial cells that received long-term exposure to high glucose (22 mmol/L). Studies using a small interfering RNA strategy demonstrated that endogenous SphK1, but not SphK2, is the major isoenzyme that was activated by high glucose. In addition, an increase in SphK1 phosphorylation was detected in a protein kinase C– and extracellular signal–regulated kinase 1/2–dependent manner, which accounts for the high glucose–induced increases in SphK activity. Importantly, inhibition of SphK1 by either a chemical inhibitor (
N
′,
N
′-dimethylsphingosine) or expression of a dominant-negative mutant of SphK1 (SphK
G82D
), or SphK1-specific small interfering RNA, strongly protected endothelial cells against high glucose–induced damage, as characterized by an attenuation in the expression of proinflammatory adhesion molecules, adhesion of leukocytes to endothelial cells, and nuclear factor κB activation. Thus, interventions that target the SphK-signaling pathway may have the potential to prevent vascular lesions under hyperglycemic conditions.
Mineralocorticoid Receptor Blocker Increases Angiotensin-Converting Enzyme 2 Activity in Congestive Heart Failure Patients
Authors: Keidar Shlomo , Gamliel-Lazarovich Aviva , Kaplan Marielle , Pavlotzky Elsa , Hamoud Shadi , Hayek Tony , Karry Rachel , Abassi Zaid
Published: September 2005

Aldosterone plays an important role in the pathophysiology of congestive heart failure (CHF), and spironolactone improves cardiovascular function and survival rates in patients with CHF. We hypothesized that the mineralocorticoid receptor blockade (MRB) exerted its beneficial effects by reducing oxidative stress and changing the balance between the counter-acting enzymes angiotensin-converting enzyme (ACE) and ACE2. Monocyte-derived macrophages were obtained from 10 patients with CHF before and after 1 month of treatment with spironolactone (25 mg/d). Spironolactone therapy significantly (
P
<0.005) reduced oxidative stress, as expressed by reduced lipid peroxide content, superoxide ion release, and low-density lipoprotein oxidation by 28%, 53%, and 70%, respectively. Although spironolactone significantly (
P
<0.01) reduced macrophage ACE activity by 47% and mRNA expression by 53%, ACE2 activity and mRNA expression increased by 300% and 654%, respectively. In mice treated for 2 weeks with eplerenone (200 mg · kg
−1
· d
−1
), cardiac ACE2 activity significantly (
P
<0.05) increased by 2-fold and was paralleled by increased ACE2 activity in macrophages. The mechanism of aldosterone antagonist action was studied in mouse peritoneal macrophages (MPMs) in vitro. Although ACE activity and mRNA were significantly increased by 250 nmol/L aldosterone, ACE2 was significantly reduced. Cotreatment with eplerenone (2 μmol/L) attenuated these effects. In MPM obtained from p47 knockout mice, where NADPH oxidase is inactive, as well as in control MPMs treated with NADPH oxidase inhibitor, aldosterone did not increase ACE or decrease ACE2. MRB reduced oxidative stress, decreased ACE activity, and increased ACE2 activity, suggesting a protective role for MRB by possibly increasing generation of angiotensin (1–7) and decreasing formation of angiotensin II. These effects are mediated, at least in part, by NADPH oxidase.
Multimodal Therapy for the Treatment of Severe Ischemic Stroke Combining GPIIb/IIIa Antagonists and Angioplasty After Failure of Thrombolysis
Authors: Abou-Chebl Alex , Bajzer Christopher T. , Krieger Derk W. , Furlan Anthony J. , Yadav Jay S.
Published: September 2005

Background and Purpose—

Intraarterial and intravenous thrombolysis are often ineffective for the treatment of acute ischemic stroke and are associated with a significant risk of intracranial hemorrhage (ICH). Multimodal rescue therapy combining mechanical disruption and platelet GPIIb/IIIa receptor antagonists may improve recanalization.

Methods—

Patients who did not recanalize with thrombolysis were treated with GPIIb/IIIa antagonists, angioplasty, or an embolectomy device. Treatment was individualized based on vascular anatomy, stroke mechanism, patient status, and symptom duration.

Results—

Twelve patients were treated within 3.8±2.2 hours. The mean National Institutes of Health Stroke Scale (NIHSS) score was 19.4±4.1. Six patients had carotid terminus occlusion, whereas 5 had middle cerebral artery and 1 had basilar artery occlusion. The average doses of intraarterial tPA and reteplase were 17.1±8.6 mg and 2±0.6 units, respectively. All patients received either an intravenous or intraarterial abciximab bolus (mean 11.8±5.8mg) and heparin (mean 3278±1716U). Eleven were treated with angioplasty and 4 had mechanical embolectomy or stenting. Complete (8) or partial (3) recanalization was achieved in 11 cases. There was only one (8.3%) symptomatic hemorrhage. Patients had a favorable outcome at discharge (mean NIHSS 8.9±8.7) and 6 (50%) had an NIHSS ≤4 at discharge.

Conclusions—

Multimodal rescue therapy was effective at recanalizing occluded cerebral vessels that failed thrombolysis without an excess risk of ICH.
Comparison of the National Institutes of Health Stroke Scale With Disability Outcome Measures in Acute Stroke Trials
Authors: Young Fiona B. , Weir Christopher J. , Lees Kennedy R.
Published: September 2005

Background and Purpose—

Acute stroke trials typically use disability scales as their primary end point. Neurologic impairment scales such as the National Institutes of Health Stroke Scale (NIHSS) are possibly more sensitive to change in patient status. We aimed to compare a range of potential NIHSS end points with modified Rankin Scale (mRS) and Barthel Index (BI) end points.

Methods—

We simulated a total of 6000 clinical trials, each with 1400 patients. We estimated statistical power for a range of NIHSS end points, including prognosis-adjusted and fixed dichotomized end points. These end points were compared with the BI and mRS dichotomized at 95 and 1, respectively.

Results—

The most powerful fixed end point was the NIHSS dichotomized at 1. For prognosis-adjusted outcome, we found greatest power if we defined success as achieving a score of ≤1 or improvement by at least 11 points from baseline. We are more likely to achieve a statistically significant result by using this prognosis-adjusted end point instead of NIHSS ≤1 (odds ratio, 2.8; 95% confidence interval [CI], 2.5 to 3.2). Use of the optimal NIHSS prognosis-adjusted end point rather than BI ≥95 could justify a reduction in sample size of approximately 68% (95% CI, 67% to 69%) without loss of statistical power.

Conclusions—

The NIHSS neurologic scale appears more sensitive than the BI or mRS, allowing smaller sample sizes or greater statistical power. The use of an NIHSS prognosis-adjusted end point could allow therapeutic effects from drugs to be more easily identified.
Blockade of Gap Junctions In Vivo Provides Neuroprotection After Perinatal Global Ischemia
Authors: de Pina-Benabou Mara H. , Szostak Vanessa , Kyrozis Andreas , Rempe David , Uziel Daniela , Urban-Maldonado Marcia , Benabou Salomon , Spray David C. , Federoff Howard J. , Stanton Patric K. , Rozental Renato
Published: September 2005

Background and Purpose—

We investigated the contribution of gap junctions to brain damage and delayed neuronal death produced by oxygen-glucose deprivation (OGD).

Methods—

Histopathology, molecular biology, and electrophysiological and fluorescence cell death assays in slice cultures after OGD and in developing rats after intrauterine hypoxia-ischemia (HI).

Results—

OGD persistently increased gap junction coupling and strongly activated the apoptosis marker caspase-3 in slice cultures. The gap junction blocker carbenoxolone applied to hippocampal slice cultures before, during, or 60 minutes after OGD markedly reduced delayed neuronal death. Administration of carbenoxolone to ischemic pups immediately after intrauterine HI prevented caspase-3 activation and dramatically reduced long-term neuronal damage.

Conclusions—

Gap junction blockade may be a useful therapeutic tool to minimize brain damage produced by perinatal and early postnatal HI.
Neuroinflammation and Both Cytotoxic and Vasogenic Edema Are Reduced in Interleukin-1 Type 1 Receptor-Deficient Mice Conferring Neuroprotection
Authors: Lazovic Jelena , Basu Anirban , Lin Hsiao-Wen , Rothstein Raymond P. , Krady J. Kyle , Smith Michael B. , Levison Steven W.
Published: September 2005

Background and Purpose—

Interleukin-1 (IL-1) is a proinflammatory cytokine implicated in multiple neurodegenerative diseases, including stroke. However, to date, there is no consensus regarding which receptor(s) mediates the detrimental effects of IL-1. We hypothesized that abrogating IL-1 type 1 receptor (IL-1R1) signaling would reduce edema, chemokine expression, and leukocyte infiltration; lower levels of iNOS; and, consequently, decrease free radical damage after mild hypoxia/ischemia (H/I), thus preserving brain cells.

Methods—

IL-1R1 null mice and wild-type mice were subjected to a mild H/I insult. MRI was used to measure the area affected at 30 minutes and 48 hours after H/I. An RNAse protection assay was used to evaluate changes in chemokine mRNA expression. RT-PCR was used to assess inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase mRNA levels. Immunohistochemistry was used to assess leukocyte infiltration. Western blots were used to assess iNOS and glutamate aspartate transporter protein levels.

Results—

IL-1R1 null mice had reduced cytotoxic and vasogenic edema. The volume of hyperintense signal on T
2
-weighted images was reduced on average by 90% at 48 hours after H/I. The induction of multiple chemokine mRNAs was significantly reduced in IL-1R1 null mice compared with wild-type mice at 18 and 72 hours after H/I, which correlated with fewer infiltrating CD3+ leukocytes. Levels of iNOS protein and mRNA (but not glutamate aspartate transporter) were significantly reduced in the IL-1R1 mouse brain.

Conclusions—

These findings indicate that abrogating IL-1R1 signaling could protect brain cells subsequent to a mild stroke by reducing edema and immune cell recruitment, as well as by limiting iNOS-mediated free radical damage.
A New Visual Rating Scale to Assess Strategic White Matter Hyperintensities Within Cholinergic Pathways in Dementia
Authors: Bocti Christian , Swartz Richard H. , Gao Fu-Qiang , Sahlas Demetrios J. , Behl Pearl , Black Sandra E.
Published: September 2005

Background and Purpose—

One possible mechanism of cognitive decline in individuals with subcortical vascular disease is disruption of cholinergic fibers by ischemic lesions, such as strategically located white matter hyperintensities (WMH). The authors applied a new MRI visual rating scale to assess WMH within cholinergic pathways in patients with Alzheimer Disease (AD) and subcortical ischemic microvascular disease.

Methods—

Subjects included 60 AD patients with and without WMH, matched for age, as well as 15 control subjects. A visual rating scale was developed based on published immunohistochemical tracings of the cholinergic pathways in humans. On 4 selected axial images, the severity of WMH in the cholinergic pathways was rated on a 3-point scale for ten regions, identified with major anatomical landmarks. A published, consensus-derived, general WMH scale was also applied. All subjects underwent standardized neuropsychological testing.

Results—

The Cholinergic Pathways HyperIntensities Scale showed reliability and was validated with volumetry of strategic WMH. After accounting for age and education in a multiple linear regression model, The Cholinergic Pathways HyperIntensities Scale ratings were associated with impaired performance on the Mattis Dementia Rating Scale (
r
=0.40;
P
=0.02) and accounted for 12% of the variance (corrected
r
2
). A similar model was not significant for general WMH scores.

Conclusions—

The new MRI rating scale for WMH in cholinergic pathways is reliable and shows stronger correlations with cognitive performance than a general WMH rating scale in AD with WMH. This new rating scale provides indirect evidence that localization of WMH within neurotransmitter systems may contribute to cognitive decline.
Culprit Factors for the Failure of Well-Conducted Warfarin Therapy to Prevent Ischemic Events in Patients With Atrial Fibrillation
Authors: Poli Daniela , Antonucci Emilia , Cecchi Emanuele , Marcucci Rossella , Liotta Agatina Alessandrello , Cellai Anna Paola , Lenti Meri , Gensini Gian Franco , Abbate Rosanna , Prisco Domenico
Published: September 2005

Background and Purpose—

In patients with atrial fibrillation (AF), oral anticoagulant therapy (OAT) is effective in reducing stroke and embolism. However, despite OAT, ischemic events do occur in some patients. Studies specifically addressing the identification of risk factors for ischemic events during well-conducted OAT are not available. In this study, we prospectively investigated the role of classic risk factors and homocysteine levels in the occurrence of ischemic complications in 364 AF patients on OAT.

Methods—

The quality of anticoagulation levels and the occurrence of bleeding and thrombotic events were recorded.

Results—

During follow-up (859 patient years) 21 patients had ischemic complications (rate 2.4×100 patient-years). Homocysteine plasma levels were higher in these patients than in patients without ischemic complications during OAT (
P
<0.01), whereas no difference was observed in relation to the quality of OAT. The presence of a history of previous ischemic events, hypertension, and homocysteine plasma levels over the 90th percentile were all associated with an increased risk of ischemic events during OAT (odds ratio [OR]=7, 4.5, and 4.7, respectively). The coexistence of these risk factors markedly increased the risk (OR=13.1; 95% CI, 3.7 to 45.7;
P
=0.001).

Conclusion—

In conclusion, our results indicate that AF patients with multiple risk factors may not be sufficiently protected by OAT, even when this is well conducted.
Statins Are Associated With Better Outcomes After Carotid Endarterectomy in Symptomatic Patients
Authors: Kennedy James , Quan Hude , Buchan Alastair M. , Ghali William A. , Feasby Thomas E.
Published: September 2005

Background and Purpose—

Statins have been associated with a reduction in mortality from noncardiac surgery. This study aimed to determine whether statin use on admission to hospital for carotid endarterectomy was associated with a reduction of in-hospital adverse outcomes.

Methods—

Data describing patient characteristics, surgical indication, statin treatment, and in-hospital outcomes of death, ischemic stroke or death and cardiac outcomes were collected from a chart review of all patients (3360) undergoing carotid endarterectomy in Western Canada from January 2000 to December 2001. Outcomes of patients on statins versus those not on statins were compared using logistic regression to account for differences in patient characteristics, and propensity score methods to account for factors influencing patient allocation to statins.

Results—

Eight hundred and fifteen of 2031 symptomatic patients and 665 of 1252 asymptomatic patients were on a statin at the time of hospital admission. Statin use by symptomatic patients was associated with reduced in-hospital mortality and in-hospital ischemic stroke or death, but not in-hospital cardiac outcomes (adjusted odds ratio 0.25 [CI, 0.07 to 0.90], 0.55 [CI, 0.32 to 0.95], 0.87 [CI, 0.49 to 1.54], respectively). The improvement in outcomes was robust when tested using propensity score matching. This association was not seen in asymptomatic patients on statins (adjusted odds ratio, in-hospital mortality 0.54 [CI, 0.13 to 2.24]; in-hospital ischemic stroke or death 1.34 [CI, 0.61 to 2.93]; in-hospital cardiac outcomes 1.37 [CI, 0.73 to 2.58]).

Conclusions—

These findings are suggestive of a protective effect of statin therapy in symptomatic patients pre-treated at the time of carotid endarterectomy, though this needs confirmation in a randomized controlled trial.
Metabolic Imaging With β-Methyl-
p
-[
123
I]-Iodophenyl-Pentadecanoic Acid Identifies Ischemic Memory After Demand Ischemia
Authors: Dilsizian Vasken , Bateman Timothy M. , Bergmann Steven R. , Des Prez Roger , Magram Martin Y. , Goodbody Anne E. , Babich John W. , Udelson James E.
Published: September 2005

Background—

After myocardial ischemia, prolonged suppression of fatty acid metabolism may persist despite restoration of blood flow, which is called metabolic stunning. We hypothesized that a branched-chain fatty acid, β-methyl-
p
-[
123
I]-iodophenyl-pentadecanoic acid (BMIPP), might identify the presence of myocardial ischemia late after demand ischemia at rest up to 30 hours later.

Methods and Results—

In 32 patients with exercise-induced ischemia on thallium SPECT, BMIPP was injected at rest within 30 hours of ischemia. SPECT images were acquired beginning 10 minutes after injection (early) and again 30 minutes after injection (delayed). Thallium and BMIPP SPECT data were read separately by 3 observers blinded to other imaging and clinical data. Agreement between BMIPP and thallium data for the presence of an abnormality on the patient level was 91% (95% CI, 75 to 98) for the early BMIPP data and 94% (95% CI, 79 to 99) for the delayed BMIPP data. Agreement between delayed BMIPP and thallium was 95% among 21 patients studied on the same day, a mean of 6.2±1.4 hours after exercise-induced ischemia, and 91% among the 11 patients studied on the next calendar day, a mean of 24.9±2.6 hours after ischemia (
P
=NS). The magnitude of resting BMIPP metabolic defect by semiquantitative visual analysis was correlated to the magnitude of exercise-induced thallium perfusion defect (
r
=0.6,
P
<0.001 for early BMIPP;
r
=0.5,
P
=0.005 for delayed BMIPP).

Conclusions—

Metabolic imaging with BMIPP identifies patients with recent exercise-induced myocardial ischemia. These findings support the concept that BMIPP imaging can successfully demonstrate the metabolic imprint of a stress-induced ischemic episode, also known as ischemic memory.
Acute Systemic Inflammation Increases Arterial Stiffness and Decreases Wave Reflections in Healthy Individuals
Authors: Vlachopoulos Charalambos , Dima Ioanna , Aznaouridis Konstantinos , Vasiliadou Carmen , Ioakeimidis Nikolaos , Aggeli Constadina , Toutouza Marina , Stefanadis Christodoulos
Published: September 2005

Background—

Aortic stiffness is a marker of cardiovascular disease and an independent predictor of cardiovascular risk. Although an association between inflammatory markers and increased arterial stiffness has been suggested, the causative relationship between inflammation and arterial stiffness has not been investigated.

Methods and Results—

One hundred healthy individuals were studied according to a randomized, double-blind, sham procedure–controlled design. Each substudy consisted of 2 treatment arms, 1 with
Salmonella typhi
vaccination and 1 with sham vaccination. Vaccination produced a significant (
P
<0.01) increase in pulse wave velocity (at 8 hours by 0.43 m/s), denoting an increase in aortic stiffness. Wave reflections were reduced significantly (
P
<0.01) by vaccination (decrease in augmentation index of 5.0% at 8 hours and 2.5% at 32 hours) as a result of peripheral vasodilatation. These effects were associated with significant increases in inflammatory markers such as high-sensitivity C-reactive protein (
P
<0.001), high-sensitivity interleukin-6 (
P
<0.001), and matrix metalloproteinase-9 (
P
<0.01). With aspirin pretreatment (1200 mg PO), neither pulse wave velocity nor augmentation index changed significantly after vaccination (increase of 0.11 m/s and 0.4%, respectively;
P
=NS for both).

Conclusions—

This is the first study to show through a cause-and-effect relationship that acute systemic inflammation leads to deterioration of large-artery stiffness and to a decrease in wave reflections. These findings have important implications, given the importance of aortic stiffness for cardiovascular function and risk and the potential of therapeutic interventions with antiinflammatory properties.
γ-Glutamyltransferase as a Risk Factor for Cardiovascular Disease Mortality
Authors: Ruttmann Elfriede , Brant Larry J. , Concin Hans , Diem Günter , Rapp Kilian , Ulmer Hanno ,   the Vorarlberg Health Monitoring and Promotion Program Study Group
Published: September 2005

Background—

There is evidence from recent studies that γ-glutamyltransferase (GGT) is likely to be associated with cardiovascular disease (CVD). However, few studies to date with sufficient sample size and follow-up investigated the association of GGT with CVD mortality.

Methods and Results—

The relation of GGT to the risk of death from CVD was examined in a cohort of 163 944 Austrian adults that was monitored for up to 17 years. To evaluate GGT as an independent predictor, Cox proportional hazards models were calculated, which adjusted for established risk factors. In both men and women, high GGT was significantly (
P
<0.001) associated with total mortality from CVD, showing a clear dose-response relationship. Adjusted hazard ratios (95% CI) per log GGT increase were 1.66 (1.40 to 1.98) in men and 1.64 (1.36 to 1.97) in women. In men, subgroup analyses showed that high GGT was positively associated with incident fatal events of chronic forms of coronary heart disease (
P
=0.009), congestive heart failure (
P
<0.001), and hemorrhagic (
P
=0.01) and ischemic stroke (
P
<0.001). No significant associations were observed for acute myocardial infarction (
P
=0.16). In women, hazard ratios suggested associations in all subgroups; however, for hemorrhagic and ischemic stroke they were not statistically significant (
P
=0.09 and
P
=0.07, respectively). In addition, subgroup analyses stratified by age revealed a stronger relationship of GGT in younger participants. Hazard ratios for total CVD were 2.03 (1.53 to 2.69) in men and 2.60 (1.53 to 4.42) in women younger than 60 years.

Conclusions—

This study demonstrates in a large, prospectively observed cohort that GGT is independently associated with cardiovascular mortality.
MASON: A Multiagent Simulation Environment
Authors: Luke Sean , Cioffi-Revilla Claudio , Panait Liviu , Sullivan Keith , Balan Gabriel
Published: September 2005

MASON is a fast, easily extensible, discrete-event multi-agent simulation toolkit in Java, designed to serve as the basis for a wide range of multi-agent simulation tasks ranging from swarm robotics to machine learning to social complexity environments. MASON carefully delineates between model and visualization, allowing models to be dynamically detached from or attached to visualizers, and to change platforms mid-run. This paper describes the MASON system, its motivation, and its basic architectural design. It then compares MASON to related multi-agent libraries in the public domain, and discusses six applications of the system built over the past year which suggest its breadth of utility.
Multiagent RoboNBA Simulation: From Local Behaviors to Global Characteristics
Authors: Hu Bingcheng , Liu Jiming , Jin Xiaolong
Published: September 2005

In this article, the authors show their current work on the relationship between local behaviors of agents and global characteristics in a multiagent NBA simulation, which is called RoboNBA. Two sources of different local behaviors are introduced: decision-making mechanisms and agent strategies. The global characteristics consist of global performance and global patterns. The authors address the problem of how to quantitatively measure the global performance and global patterns in RoboNBA. For global patterns, they focus on the diversity of attack patterns of a team. Through experiments and analysis, they try to examine how agent local behaviors can lead to different global performance and interesting global patterns in RoboNBA.
On-Line Stability Margin and Attitude Estimation for Dynamic Articulating Mobile Robots
Authors: Diaz-Calderon Antonio , Kelly Alonzo
Published: September 2005

Stability is an important concern for vehicles which move heavy loads, accelerate or brake aggressively, turn at speed, or operate on sloped terrain. In many cases, vehicles face more than one of these challenges simultaneously. Some are obliged to execute these maneuvers when their high centers of gravity leave them particularly vulnerable to tipover or rollover. A methodology is presented to estimate proximity to tipover for autonomous field robots that must be productive, effective, and self-reliant under such challenging circumstances. While the physical principles governing the computation of stability margin have been known for some time, the realization of these principles in practice raises issues which are at once similar to those of attitude estimation while contrasting heavily with inertial guidance. The problem of stability margin estimation is posed in the fairly general case of accelerated articulating motion over rough terrain. Compatibility with and distinctions from attitude estimation lead to a proposed integrated solution to both problems based on the fusion of inertial, articulation, and terrain relative velocity sensing in an optimal estimation framework. An implementation of a device targeted to an industrial lift truck is presented.
Approximating Kinematics for Tracked Mobile Robots
Authors: Martínez J. L. , Mandow A. , Morales J. , Pedraza S. , García-Cerezo A.
Published: September 2005

In this paper we propose a kinematic approach for tracked mobile robots in order to improve motion control and pose estimation. Complex dynamics due to slippage and track–soil interactions make it difficult to predict the exact motion of the vehicle on the basis of track velocities. Nevertheless, real-time computations for autonomous navigation require an effective kinematics approximation without introducing dynamics in the loop. The proposed solution is based on the fact that the instantaneous centers of rotation (ICRs) of treads on the motion plane with respect to the vehicle are dynamics-dependent, but they lie within a bounded area. Thus, optimizing constant ICR positions for a particular terrain results in an approximate kinematic model for tracked mobile robots. Two different approaches are presented for off-line estimation of kinematic parameters: (i) simulation of the stationary response of the dynamic model for the whole velocity range of the vehicle; (ii) introduction of an experimental setup so that a genetic algorithm can produce the model from actual sensor readings. These methods have been evaluated for on-line odometric computations and low-level motion control with the Auriga-α mobile robot on a hard-surface flat soil at moderate speeds.
The Black radical tradition - theory and practice: Black studies and the scholarship of Cedric Robinson
Authors: Thomas Darryl C.
Published: September 2005

Cedric Robinson’s scholarship and radical pedagogy are explored here, within the context of the development of Black studies in the US academy and the challenge that this posed to the ‘master narratives’ of Eurocentric scholarship. The emergence of Robinson’s works and his development of the concept of racial capitalism were integral to the political thrust of Black studies. His Black Marxism, in particular, not only identified and analysed earlier major radical theorists of the Black condition, but also located a hitherto subterranean, yet always existent and insistent, Black radical tradition. The continuing influence of Robinson’s historical and philosophical works on subsequent scholarship is outlined, as is the importance of creating a sustainable community of scholars to carry on the radical tradition.
Reflections on Black Marxism
Authors: Tatum Travis
Published: September 2005

Cedric Robinson’s work on the Black radical tradition is, in effect, a challenge to the basic cultural and social assumptions of western society. These assumptions - the underlying ‘terms of order’ holding society together - limit our perception of the choices that are available to us, even seeping into programmes for radical change, such as Marxism. But by recovering the hidden histories of resistance by those on the margins of capitalism, in this case in the African diaspora, we can move beyond the misconceptions and myths that bind us to power.
The Black radical tradition and the academy: The future of radical scholarship
Authors: Gordon Avery F.
Published: September 2005

What is the essence of radical scholarship? How does it relate to subjugated knowledge and those experiences historically dismissed as of little account? Its relationship to truth telling and its attempt to extend the boundaries of what is known and knowable are here discussed in relation to Robinson’s lifetime work. It is grounded both in a refusal to compromise and, in Robinson’s phrase, in ‘the recovery of human life from the spoilage of degradation’.
On Cedric Robinson and Black Marxism: a view from the US academy
Authors: Plummer Brenda Gayle
Published: September 2005

Cedric Robinson’s directorship of the Center for Black Studies at the University of California Santa Barbara reflected his genius as a radical communitarian during an era in which the US academy as a whole set itself on a path of increasing cultural and social isolation from mainstream society. As an academic enterprise, the Center mirrors the radical conservationism inherent in Black Marxism’s recuperation of the Black radical tradition.
X-treme Group Analysis: On the Countertransference Edge in Inpatient Work with Forensic Patients
Authors: Gordon John , Harding Sharman , Miller Claire , Xenitidis Kiriakos
Published: September 2005

Setting up analytic psychotherapy groups on secure forensic wards is a complicated and arduous process. Once established, clinical work is even more difficult because emotional contact with forensic patients places extreme pressure on the countertransference. We review aspects of the psychoanalytic theory of countertransference related to increasingly serious levels of psychopathology in order to clarify why this should be so. Examples of clinical group analysis and work with forensic staff illustrate our experiences on the countertransference edge.
Effects of the Degree of Deacetylation on the Physicochemical Properties and Schwann Cell Affinity of Chitosan Films
Authors: Wenling Cao , Duohui Jing , Jiamou Li , Yandao Gong , Nanming Zhao , Xiufang Zhang
Published: September 2005

Chitosan is a potential material for the preparation of nerve repair conduits. In order to find a better chitosan for the application in peripheral nerve regeneration, the effects of the degree of deacetylation (DD) on the physicochemical properties and Schwann cell affinity of chitosan films have been evaluated. Six kinds of chitosan samples with similar molecular weight, but various DD in a range from 70.1 to 95.6% were prepared from one stock chitosan material and fabricated into films. X-ray diffraction analysis showed that there were more crystalline regions in the higher DD chitosan films. Swelling and mechanical property measurements revealed that the swelling index of chitosan films decreased and their elastic modulus and tensile strength increased with the increase in DD. The adsorption amount of fibronectin and laminin on chitosan films was measured by means of enzyme-linked immunosorbent assay (ELISA). Culture of adult rat Schwann cells on the films showed that the chitosan films with higher DD provided better substrata for Schwann cell spreading and proliferation. In conclusion, DD of chitosan plays an important role in their physicochemical properties and affinity with Schwann cells. The results suggest that chitosan with a DD higher than 90% is considered as a promising material for application in peripheral nerve regeneration.
Mother Goose, Spud Murphy and the Librarian Knights
Authors: Maynard Sally , McKenna Fiona
Published: September 2005

This article investigates the ways in which libraries and librarians are portrayed in children’s fiction. Three example texts are used to determine whether the portrayal of the library and the librarian in modern children’s fiction provides children with a positive image of the service, and to identify the ways in which such fiction can teach children about library use. The chosen texts provide critical analysis and are as follows: Little Bo Peep’s Library Book (Cowell, 1999); The Legend of Spud Murphy (Colfer, 2004) and The Last of the Sky Pirates (Stewart and Riddell, 2003). The three texts include a picture book for young children, a story for children who are capable of reading on their own and a book for older children and young adults. The main conclusion drawn is that modern children’s fiction presents a positive view of libraries, librarians and the services they provide. It is argued that a variety of methods is used to portray libraries and librarians in a positive light, and that such fiction may play a considerable role in educating young readers about responsible library use and the range of services provided by libraries.