bluuebunny/crossref_metadata_2025 huggingface dataset:
Attenuation of Graft Arterial Disease by Manipulation of the LIGHT Pathway
Authors: Kosuge Hisanori , Suzuki Jun-ichi , Kakuta Tsunekazu , Haraguchi Go , Koga Noritaka , Futamatsu Hideki , Gotoh Ryo , Inobe Manabu , Isobe Mitsuaki , Uede Toshimitsu
Published: June 2004

Objective—The tumor necrosis factor (TNF) superfamily member LIGHT, which binds herpes virus entry mediator (HVEM) and lymphotoxin β receptor (LTβR), plays important roles in regulating the immune response. To clarify the mechanism underlying graft arterial disease (GAD), we investigated the role of the LIGHT pathway in the progression of GAD.

Methods and Results—Hearts from Bm12 mice were transplanted into C57BL/6 (B/6) mice (class II mismatch). Recipients were injected intraperitoneally with HVEMIg (100 μg per treatment) every 7 days for 8 weeks. Treatment with HVEMIg significantly attenuated GAD (luminal occlusion=16.5±7.7% versus control allograft=62.6±12.1%,P<0.05), and significantly decreased intragraft IL-4, IL-6, and interferon-γ (IFN-γ) mRNA expression compared with controls. LTβR was expressed in smooth muscle cells (SMCs) with or without cytokine stimulation, whereas HVEM was detected in SMCs stimulated by IFN-γ. Coculture of SMCs with T cells after transplantation induced SMC proliferation, and addition of HVEMIg resulted in inhibition of SMC proliferation.

Conclusions—These results indicate that the LIGHT pathway plays important roles in the regulation not only of T-cell activation but also of SMC proliferation. Blockade of the LIGHT pathway is a promising avenue for the prevention of GAD.
Impaired Endothelium-Dependent Flow-Mediated Vasodilation in Hypertensive Subjects With Hyperaldosteronism
Authors: Nishizaka Mari K. , Zaman M. Amin , Green Sharon A. , Renfroe Kerry Y. , Calhoun David A.
Published: June 2004

Background—

Recent studies suggest that aldosterone may impair endothelium-dependent vascular function through suppression of nitric oxide formation. Assessments of forearm blood flow or arterial compliance suggest a similar effect in humans. The present study was designed to determine whether chronic aldosterone excess in subjects with resistant hypertension impairs endothelium-dependent vascular reactivity as indexed by direct assessment of brachial artery flow-mediated dilation (FMD).

Methods and Results—

Consecutive subjects (n=80) with resistant hypertension were prospectively evaluated with an early-morning ratio of plasma aldosterone to plasma renin activity and 24-hour urinary aldosterone and sodium. Changes in brachial artery diameter during reactive hyperemia were measured by high-resolution ultrasound. Hyperaldosteronism was diagnosed on the basis of a renin activity <1.0 ng · mL
−1
· h
−1
, urinary aldosterone >12 μg/24 h, and urinary sodium >200 mEq/24 h. FMD was significantly lower in 36 subjects with hyperaldosteronism (1.8±1.3% versus 3.9±1.9% from baseline;
P
<0.0001) compared with the 44 subjects without hyperaldosteronism. FMD was negatively and significantly correlated with plasma aldosterone (
r
=−0.38,
P
=0.0006), 24-hour urinary aldosterone (
r
=−0.49,
P
<0.0001), and ratio of plasma aldosterone to plasma renin activity (
r
=−0.43,
P
<0.0001) but was independent of blood pressure, age, and body mass index. In 30 subjects, 3 months of treatment with spironolactone significantly increased FMD (2.5±1.7 versus 6.0±2.0%;
P
<0.0001) independently of blood pressure change.

Conclusions—

These data demonstrate a strong association between aldosterone excess and impaired endothelial function in human subjects as indexed by flow-mediated arterial vasodilation. These results suggest that chronic aldosteronism may have a blood pressure–independent effect on cardiovascular disease progression in subjects with resistant hypertension.
Lipid-Rich Atherosclerotic Plaques Detected by Gadofluorine-Enhanced In Vivo Magnetic Resonance Imaging
Authors: Sirol Marc , Itskovich Vitalii V. , Mani Venkatesh , Aguinaldo Juan Gilberto S. , Fallon John T. , Misselwitz Bernd , Weinmann Hanns-Joachim , Fuster Valentin , Toussaint Jean-François , Fayad Zahi A.
Published: June 2004

Background—

MRI of specific components in atherosclerotic plaque may provide information on plaque stability and its potential to rupture. We evaluated gadofluorine in atherosclerotic rabbits using a new MR sequence that allows plaque detection within 1 hour after injection and assessed enhancement in lipid-rich and non–lipid-rich plaques.

Methods and Results—

Twelve rabbits with aortic plaque and 6 controls underwent MRI before and up to 24 hours after gadofluorine injection (50 μmol/kg). Two T1-weighted, segmented gradient-echo sequences (TFL) were compared to enhance vessel wall delineation after injection: (1) an inversion-recovery prepulse (IR-TFL) or (2) a combination of inversion-recovery and diffusion-based flow suppression prepulses (IR-DIFF-TFL). With the use of IR-TFL at 1 hour after injection, the vessel wall was not delineated because of poor flow suppression; at 24 hours after injection, the enhancement was 37% (
P
<0.01). IR-DIFF-TFL showed significant enhancement after versus before contrast (1 hour: 164% [
P
<0.005]; 24 hours: 207% [
P
<0.001]). At 1 hour and 24 hours after injection, the contrast-to-noise ratio was higher with the use of IR-DIFF-TFL than with IR-TFL (1 hour: 13.0±7.7 versus −19.8±10.3 [
P
<0.001]; 24 hours: 15.2±5.9 versus 11.4±8.9, respectively [
P
=0.052]). There was no enhancement in the vessel wall after gadofluorine injection in the control group. A strong correlation was found (
r
2
=0.87;
P
<0.001) between the lipid-rich areas in histological sections and signal intensity in corresponding MR images. This suggests a high affinity of gadofluorine for lipid-rich plaques.

Conclusions—

Gadofluorine-enhanced MRI improves atherosclerotic plaque detection. The IR-DIFF-TFL method allows early detection of atherosclerotic plaque within 1 hour after gadofluorine injection.
Ultrasound Strain Imaging of Altered Myocardial Stiffness
Authors: Pislaru Cristina , Bruce Charles J. , Anagnostopoulos Peter C. , Allen Jill L. , Seward James B. , Pellikka Patricia A. , Ritman Erik L. , Greenleaf James F.
Published: June 2004

Background—

In this study we evaluate the diastolic deformation of ischemic/reperfused myocardium and relate this deformation to tissue elastic properties.

Methods and Results—

Farm pigs were subjected to left anterior descending coronary artery occlusion followed by reperfusion to create either stunning (n=12) or transmural myocardial infarction (n=12). Ultrasound-derived radial strain rates (SR) and strain were measured in the ischemic and remote walls. Myocardial stiffness was estimated from diastolic pressure–wall thickness relationship obtained from preload alterations. At reperfusion, end-systolic strain (ε
sys
) was significantly reduced in both stunned and infarcted walls compared with their remote walls (3±3% versus 26±2% and 1±0% versus 33±5%, respectively;
P
<0.0001) or baseline values. Diastolic passive deformation (ε
A
) and rates of deformation during early (E
SR
) and late (A
SR
) diastole were comparable between stunned and remote walls (ε
A
: 7.3±1.6% versus 7.9±1.9%; E
SR
: −2.7±0.4 s
−1
versus −2.6±0.5 s
−1
; A
SR
: −1.8±0.2 s
−1
versus −1.9±0.3 s
−1
;
P
=NS for all) but were of significantly lower magnitude in infarcted walls versus remote walls (ε
A
: 1.1±0.2% versus 11.4±1.9%; E
SR
: −0.3±0.1 s
−1
versus −2.4±0.4 s
−1
; A
SR
: −0.3±0.1 s
−1
versus −2.5±0.4 s
−1
;
P
<0.0001 for all). Stiffness coefficient of exponential diastolic pressure–wall thickness relation was higher for infarcted (
P
<0.05) but not for stunned walls (
P
=NS) compared with their remote walls.

Conclusions—

Early after postischemic reperfusion and in the presence of severely reduced systolic deformation, diastolic passive deformation (and rates of deformation) can distinguish stiff, noncompliant, transmurally infarcted myocardial walls from those more compliant walls containing viable but stunned myocardium.
Impaired Baroreceptor Control of Renal Sympathetic Activity in Human Chronic Heart Failure
Authors: Al-Hesayen Abdul , Parker John D.
Published: June 2004

Background—

The regulation of renal sympathetic activity in the setting of heart failure is largely unexplored. We used the norepinephrine spillover method to address the hypothesis that baroreflex control of renal sympathetic activity is blunted in heart failure.

Methods and Results—

Twenty-two patients were studied, 11 in a group with heart failure and 11 in a group with normal ventricular function. In both groups, renal norepinephrine spillover was assessed in response to sodium nitroprusside infused to steady-state conditions. Sodium nitroprusside resulted in significant reductions in mean systemic arterial pressure (normal group, −13±1% [mean±SEM]; heart failure group, −12±1%). In response to nitroprusside, there was an 85±34% increase in renal norepinephrine spillover in the normal group (from 537±84 to 840±140 pmol/min,
P
<0.05). Despite similar hemodynamic responses to nitroprusside in the heart failure group, renal norepinephrine spillover was unchanged (from 1420±153 to 1387±161 pmol/min,
P
=NS), a response that was significantly different from that seen in the normal group.

Conclusions—

In patients with heart failure, compared with those with normal ventricular function, renal sympathetic activity did not change in response to a steady-state infusion of sodium nitroprusside. This result provides evidence for reduced baroreflex control of renal sympathetic activity in heart failure.
Changes in Atrial Fibrillation Cycle Length and Inducibility During Catheter Ablation and Their Relation to Outcome
Authors: Haïssaguerre Michel , Sanders Prashanthan , Hocini Mélèze , Hsu Li-Fern , Shah Dipen C. , Scavée Christophe , Takahashi Yoshihide , Rotter Martin , Pasquié Jean-Luc , Garrigue Stéphane , Clémenty Jacques , Jaïs Pierre
Published: June 2004

Background—

The modification of atrial fibrillation cycle length (AFCL) during catheter ablation in humans has not been evaluated.

Methods and Results—

Seventy patients undergoing ablation of prolonged episodes of AF were randomized to pulmonary vein (PV) isolation or additional ablation of the mitral isthmus. Mean AFCL was determined at a distance from the ablated area (coronary sinus) at the following intervals: before ablation, after 2- and 4-PV isolations, and after linear ablation. Inducibility of sustained AF (≥10 minutes) was determined before and after ablation. Spontaneous sustained AF (715±845 minutes) was present in 30 patients and induced in 26 (AFCL, 186±19 ms). PV isolation terminated AF in 75%, with the number of PVs requiring isolation before termination increasing with AF duration (
P
=0.018). PV isolation resulted in progressive or abrupt AFCL prolongation to various extents, depending on the PV: to 214±24 ms (
P
<0.0001) when AF terminated and to 194±19 ms (
P
=0.002) when AF persisted. The increase in AFCL (30±17 versus 14±11 ms;
P
=0.005) and the decrease in fragmentation (30.0±26.8% to 10.3±14.5%;
P
<0.0001) were significantly greater in patients with AF termination. Linear ablation prolonged AFCL, with a greater prolongation in patients with AF termination (44±13 versus 22±23 ms;
P
=0.08). Sustained AF was noninducible in 57% after PV isolation and in 77% after linear ablation. At 7±3 months, 74% with PV isolation and 83% with linear ablation were arrhythmia free without antiarrhythmics, which was significantly associated with noninducibility (
P
=0.03) with a recurrence rate of 38% and 13% in patients with and without inducibility, respectively.

Conclusions—

AF ablation results in a decline in AF frequency, with a magnitude correlating with termination of AF and prevention of inducibility that is predictive of subsequent clinical outcome.
Inflammation as a Possible Link Between Coronary and Carotid Plaque Instability
Authors: Lombardo Antonella , Biasucci Luigi Marzio , Lanza Gaetano Antonio , Coli Stefano , Silvestri Pasquale , Cianflone Domenico , Liuzzo Giovanna , Burzotta Francesco , Crea Filippo , Maseri Attilio
Published: June 2004

Background—

Multiple complex stenoses, plaque fissures, and widespread coronary inflammation are common in acute coronary syndromes. A systemic cause of atherosclerotic plaque instability is also suggested by studies of ischemic cerebrovascular disease. We investigated the association between coronary and carotid plaque instability and the potential common causal role of inflammation.

Methods and Results—

The ultrasound characteristics of carotid plaques were evaluated retrospectively in patients scheduled for coronary bypass surgery, 181 with unstable and 92 with stable angina, and prospectively in a similar group of patients, 67 with unstable and 25 with stable angina, in whom serum C-reactive protein levels were also measured. The prevalence of carotid plaques was similar in the retrospective and prospective studies and >64% in both unstable and stable coronary patients. The prevalence of complex, presumably unstable carotid plaques was 23.2% in unstable versus 3.2% in stable patients (
P
<0.001) in the retrospective study and 41.8% versus 8.0% (
P
=0.002) in the prospective study. C-reactive protein levels were higher in patients with complex (7.55 mg/L) than in those with simple (3.94 mg/L;
P
<0.05) plaques or without plaques (2.45 mg/L;
P
<0.05). On multivariate analysis, unstable angina and C-reactive protein levels >3 mg/L were independently associated with complex carotid plaques (OR, 6.09; 95% CI, 1.01 to 33.72;
P
=0.039, and OR, 5.80; 95% CI, 1.55 to 21.69;
P
=0.009, respectively).

Conclusions—

In unstable angina, plaque instability may not be confined to coronary arteries, and inflammation may be the common link with carotid plaque instability. These observations may have relevant implications for understanding the mechanisms of acute widespread atherothrombotic plaque inflammation.
Plasma Brain Natriuretic Peptide to Detect Preclinical Ventricular Systolic or Diastolic Dysfunction
Authors: Redfield Margaret M. , Rodeheffer Richard J. , Jacobsen Steven J. , Mahoney Douglas W. , Bailey Kent R. , Burnett John C.
Published: June 2004

Background—

Preclinical systolic or diastolic dysfunction is associated with increased morbidity and mortality. We postulated that plasma brain natriuretic peptide (BNP) might serve as a biomarker for preclinical ventricular dysfunction (PCVD) but that the discriminatory values for BNP may vary with age and sex.

Methods and Results—

We measured BNP, systolic and diastolic ventricular function, and clinical parameters in 2042 randomly selected residents of Olmsted County, Minn, aged 45 years or older. For preclinical systolic dysfunction, the areas under the receiver operating characteristics curve were higher for those with more severe (0.82 to 0.92) than any (0.51 to 0.74) systolic dysfunction and were similar in men and women and in younger and older persons. For preclinical diastolic dysfunction, the areas under the receiver operating characteristics curve were higher for those with moderate-to-severe (0.74 to 0.79) than any (0.52 to 0.68) diastolic dysfunction and were similar regardless of age or sex. Optimal discriminatory values of BNP varied with age and sex. Considering the prevalence of preclinical systolic or diastolic dysfunction and the predictive characteristics observed, using BNP to screen for PCVD would necessitate echo in 10% to 40% of those screened, with most confirmatory echocardiograms being negative, and would miss 10% to 60% of those affected.

Conclusions—

BNP is a suboptimal screening test for PCVD in the population.
Clinical Assessment of Norepinephrine Transporter Blockade Through Biochemical and Pharmacological Profiles
Authors: Vincent Simi , Bieck Peter R. , Garland Emily M. , Loghin Corina , Bymaster Frank P. , Black Bonnie K. , Gonzales Celedon , Potter William Z. , Robertson David
Published: June 2004

Background—

To assess the sensitivity of biochemical, physiological, and pharmacological markers of peripheral norepinephrine (NE) transporter (NET) function, we chronically antagonized NET by a range of doses of duloxetine [(+)-
N
-methyl-3-(1-naphthalenyloxy)-2 thiophenepropanamine], which blocks the NE reuptake process.

Methods and Results—

Duloxetine was administered in a randomized, placebo-controlled study in 15 healthy volunteers. Plasma from duloxetine-treated subjects (ex vivo effect) dose-dependently decreased radioligand binding to human NET (maximum inhibition was 60%) (
P
=0.02). The dose of intravenous tyramine required to raise systolic blood pressure by 30 mm Hg (PD
30
) increased dose-dependently with duloxetine and was significant at the end of the 120-mg/d dosage (
P
<0.001). The plasma dihydoxyphenylglycol to NE (DHPG/NE) ratio was reduced significantly at 2 weeks of treatment with 80 mg/d duloxetine (11.3 at baseline, 3.4 at 240 mg/d,
P
<0.001). Plasma NE was significantly increased starting at 120 mg/d duloxetine. Urine results (corrected for 24-hour creatinine excretion) showed a dose-dependent change from the baseline urinary excretion for NE, DHPG, and the DHPG/NE ratio. The most sensitive measure, the DHPG/NE ratio, was significant at the 80-mg dose. Urinary NE excretion was significantly raised after 2 weeks of treatment with 80 mg/d duloxetine (
P
<0.001), the lowest dose used in the study.

Conclusions—

These findings suggest that the degree of NET blockade can be assessed with the plasma or urine DHPG/NE ratio and the pressor effect of tyramine. Also, the DHPG/NE ratio is more sensitive at the lower end of NET inhibition, whereas tyramine exhibits a linear relation, with NET inhibition commencing at a higher dose.
In Situ Measurements of Crossbridge Dynamics and Lattice Spacing in Rat Hearts by X-Ray Diffraction
Authors: Pearson James T. , Shirai Mikiyasu , Ito Haruo , Tokunaga Noriyuki , Tsuchimochi Hirotsugu , Nishiura Naoki , Schwenke Daryl O. , Ishibashi-Ueda Hatsue , Akiyama Ryuichi , Mori Hidezo , Kangawa Kenji , Suga Hiroyuki , Yagi Naoto
Published: June 2004

Background—

Synchrotron radiation has been used to analyze crossbridge dynamics in isolated papillary muscle and excised perfused hearts with the use of x-ray diffraction techniques. We showed that these techniques can detect regional changes in rat left ventricle contractility and myosin lattice spacing in in situ ejecting hearts in real time. Furthermore, we examined the sensitivity of these indexes to regional ischemia.

Methods and Results—

The left ventricular free wall of spontaneously beating rat hearts (heart rate, 290 to 404 bpm) was directly exposed to brief high-flux, low-emittance x-ray beams provided at SPring-8. Myosin mass transfer to actin filaments was determined as the decrease in reflection intensity ratio (intensity of 1,0 plane over the 1,1 plane) between end-diastole and end-systole. The distance between 1,0 reflections was converted to a lattice spacing between myosin filaments. We found that mass transfer (mean, 1.71±0.09 SEM, n=13 hearts) preceded significant increases in lattice spacing (2 to 5 nm) during systole in nonischemic pericardium. Left coronary occlusion eliminated increases in lattice spacing and severely reduced mass transfer (
P
<0.01) in the ischemic region.

Conclusions—

Our results suggest that x-ray diffraction techniques permit real-time in situ analysis of regional crossbridge dynamics at molecular and fiber levels that might also facilitate investigations of ventricular output regulation by the Frank-Starling mechanism.
Effect of Irbesartan Versus Atenolol on Left Ventricular Mass and Voltage
Authors: Schneider Markus P. , Klingbeil Arnfried U. , Delles Christian , Ludwig Malte , Kolloch Rainer E. , Krekler Michael , Stumpe Klaus O. , Schmieder Roland E.
Published: June 2004

Regression of hypertensive left ventricular hypertrophy (LVH) is associated with improved prognosis. The aim of this trial was to compare the effects of irbesartan versus atenolol on LVH in subjects with essential hypertension. Because electrocardiographic and echocardiographic parameters of LVH carry disparate prognostic information, both methods were applied in this trial. In the randomized, double-blind, multicenter trial CardioVascular Irbesartan Project, 240 patients with essential hypertension were treated with irbesartan or atenolol for 18 months. Voltage criteria used for LVH were Sokolow index, Cornell index, Cornell voltage×QRS duration product and Lewis index. In parallel, left ventricular mass (LVM) was determined by 2-dimensional guided M-mode echocardiography. After 6 and 18 months, reductions of LVM and voltage criteria for LVH were only found in subjects treated with irbesartan. However, a reduction of LVM was only detectable in subjects within the highest quartile of baseline LVM but not overall. In contrast, reductions of voltage criteria for LVH were detectable after 6 and 18 months even within commonly used normal limits. In conclusion, treatment of hypertension with irbesartan resulted in a significant reduction in the voltage criteria for LVH, although an effect on LVM was only seen in subjects with high baseline LVM. In contrast, atenolol did not lead to reductions in electrocardiographic or echocardiographic parameters of LVH. Because voltage criteria for LVH have been shown to predict cardiovascular outcome independently from LVM, we suggest that both methods should be used to accurately assess the benefits of antihypertensive treatment.
Biology of Cardiac Arrhythmias
Authors: Delisle Brian P. , Anson Blake D. , Rajamani Sridharan , January Craig T.
Published: June 2004

The mechanisms underlying normal and abnormal cardiac rhythms are complex and incompletely understood. Through the study of uncommon inheritable arrhythmia syndromes, including the long QT and Brugada syndromes, new insights are emerging. At the cellular and tissue levels, we now recognize that ion channel current is the sum of biophysical (gating, permeation), biochemical (phosphorylation, etc), and biogenic (biosynthesis, processing, trafficking, and degradation) properties. This review focuses on how heart cells process ion channel proteins and how this protein trafficking may be altered in some cardiac arrhythmia diseases. In this review, we honor Dr Harry A. Fozzard, a modern pioneer in cardiac arrhythmias, cell biology, and molecular electrophysiology. As a scientist and physician, his writings and mentorship have served to foster a generation of investigators who continue to bring this complex field toward greater scientific understanding and impact on humankind.
Atorvastatin Restores Endothelial Function in Normocholesterolemic Smokers Independent of Changes in Low-Density Lipoprotein
Authors: Beckman Joshua A. , Liao James K. , Hurley Shauna , Garrett Leslie A. , Chui Daoshan , Mitra Debi , Creager Mark A.
Published: June 2004

Cigarette smoking impairs endothelial function. Hydroxymethylglutaryl (HMG) CoA reductase inhibitors (statins) may favorably affect endothelial function via nonlipid mechanisms. We tested the hypothesis that statins would improve endothelial function independent of changes in lipids in cigarette smokers. Twenty normocholesterolemic cigarette smokers and 20 matched healthy control subjects were randomized to atorvastatin 40 mg daily or placebo for 4 weeks, washed out for 4 weeks, and then crossed-over to the other treatment. Baseline low-density lipoprotein (LDL) levels were similar in smokers and healthy subjects, 103±22 versus 95±27 mg/dL, respectively (
P
=NS) and were reduced similarly in smokers and control subjects by atorvastatin, to 55±30 and 58±20 mg/dL, respectively (
P
=NS). Vascular ultrasonography was used to determine brachial artery, flow-mediated, endothelium-dependent, and nitroglycerin-mediated, endothelium-independent vasodilation. To elucidate potential molecular mechanisms that may account for changes in endothelial function, skin biopsy specimens were assayed for eNOS mRNA, eNOS activity, and nitrotyrosine. Endothelium-dependent vasodilation was less in smokers than nonsmoking control subjects during placebo treatment, 8.0±0.6% versus 12.1±1.1%, (
P
=0.003). Atorvastatin increased endothelium-dependent vasodilation in smokers to 10.5±1.3% (
P
=0.017 versus placebo) but did not change endothelium-dependent vasodilation in control subjects (to 11.0±0.8%,
P
=NS). Endothelium-independent vasodilation did not differ between groups during placebo treatment and was not significantly affected by atorvastatin. Multivariate analysis did not demonstrate any association between baseline lipid levels or the change in lipid levels and endothelium-dependent vasodilation. Cutaneous nitrotyrosine levels and skin microvessel eNOS mRNA, but not ENOS activity, were increased in smokers compared with controls but unaffected by atorvastatin treatment. Atorvastatin restores endothelium-dependent vasodilation in normocholesterolemic cigarette smokers independent of changes in lipids. These results are consistent with a lipid-independent vascular benefit of statins but could not be explained by changes in eNOS message and tissue oxidative stress. These findings implicate a potential role for statin therapy to restore endothelial function and thereby investigate vascular disease in cigarette smokers.
Fluorescence Resonance Energy Transfer–Based Analysis of cAMP Dynamics in Live Neonatal Rat Cardiac Myocytes Reveals Distinct Functions of Compartmentalized Phosphodiesterases
Authors: Mongillo Marco , McSorley Theresa , Evellin Sandrine , Sood Arvind , Lissandron Valentina , Terrin Anna , Huston Elaine , Hannawacker Annette , Lohse Martin J. , Pozzan Tullio , Houslay Miles D. , Zaccolo Manuela
Published: June 2004

Cardiac myocytes have provided a key paradigm for the concept of the compartmentalized cAMP generation sensed by AKAP-anchored PKA. Phosphodiesterases (PDEs) provide the sole route for degrading cAMP in cells and are thus poised to regulate intracellular cAMP gradients. PDE3 and PDE4 represent the major cAMP degrading activities in rat ventriculocytes. By performing real-time imaging of cAMP in situ, we establish the hierarchy of these PDEs in controlling cAMP levels in basal conditions and on stimulation with a β-adrenergic receptor agonist. PDE4, rather than PDE3, appears to be responsible for modulating the amplitude and duration of the cAMP response to beta-agonists. PDE3 and PDE4 localize to distinct compartments and this may underpin their different functional roles. Our findings indicate the importance of distinctly localized PDE isoenzymes in determining compartmentalized cAMP signaling.
Age at Natural Menopause and Stroke Mortality
Authors: Jacobsen Bjarne K. , Heuch Ivar , Kvåle Gunnar
Published: June 2004

Background and Purpose—

Young age at natural menopause has been related to increased cardiovascular mortality, but few studies have examined the relationship with stroke risk specifically.

Methods—

In a cohort of 19 731 Norwegian women, we analyzed the relationship between age at natural menopause and stroke mortality. A total of 3561 women died of stroke during the 37-year follow-up from 1961 through 1997. Smoking prevalence was low in the underlying population, and use of hormone replacement therapy was very rare.

Results—

No significant linear relationship was found between age at menopause and stroke mortality. A 3-year increase in age at menopause was associated with a 1.0% estimated increase in stroke mortality (95% CI, −1.5, 3.6). No relationships were found for ischemic strokes (271 deaths) or hemorrhagic strokes (389 deaths) when considering the stroke deaths with sufficient information on death certificates. The estimate of the association between age at natural menopause and stroke mortality was hardly influenced by mortality in women with very early (aged <40 years) or late (aged >55 years) menopause, or by a number of possible confounding variables.

Conclusions—

Age at natural menopause is essentially unrelated to stroke mortality.
Cerebral Vascular Dysfunction Mediated by Superoxide in Hyperhomocysteinemic Mice
Authors: Dayal Sanjana , Arning Erland , Bottiglieri Teodoro , Böger Rainer H. , Sigmund Curt D. , Faraci Frank M. , Lentz Steven R.
Published: June 2004

Background and Purpose—

Hyperhomocysteinemia is an emerging risk factor for stroke, but little is known about effects of hyperhomocysteinemia on cerebral vascular function. We tested the hypothesis that chronic hyperhomocysteinemia in mice causes endothelial dysfunction in cerebral arterioles through a mechanism that involves superoxide.

Methods—

Mice heterozygous for a targeted disruption of the cystathionine β-synthase gene (
Cbs
+/−) and their wild type littermates (
Cbs
+/+) were fed either a control diet or a high-methionine diet for 10 to 12 months.

Results—

Plasma total homocysteine was elevated with the high-methionine diet compared with the control diet for both
Cbs
+/+ (7.9±1.0 versus 5.0±0.5 μmol/L;
P
<0.05) and
Cbs
+/− (20.5±3.1 versus 8.2±0.9 μmol/L;
P
<0.001) mice. Dilatation of cerebral arterioles (≈30 μm baseline diameter) was measured in vivo in response to the endothelium-dependent dilator acetylcholine or the endothelium-independent dilator nitroprusside. Vasodilatation to acetylcholine was impaired with the high-methionine diet compared with the control diet for both
Cbs
+/+ and
Cbs
+/− mice (
P
<0.01). Dilatation of arterioles to acetylcholine was restored toward normal by the superoxide scavenger tiron (
P
<0.05). Vasodilatation to nitroprusside was not influenced by
Cbs
genotype or diet. Dihydroethidium (DHE) staining for vascular superoxide was elevated in
Cbs
+/− mice fed the high-methionine diet and was inhibited by apocynin or Nω-nitro-
l
-arginine methyl ester, implicating NAD(P)H oxidase and nitric oxide synthase as potential sources of superoxide.

Conclusions—

Superoxide is a key mediator of endothelial dysfunction in the cerebral circulation during diet-induced hyperhomocysteinemia.
Perihematomal Edema in Primary Intracerebral Hemorrhage Is Plasma Derived
Authors: Butcher Ken S. , Baird Tracey , MacGregor Lachlan , Desmond Patricia , Tress Brian , Davis Stephen
Published: June 2004

Background and Purpose—

The mechanisms of perihematomal injury in primary intracerebral hemorrhage (ICH) are incompletely understood. An MRI study was designed to elucidate the nature of edema and blood flow changes after ICH.

Methods—

Perihematomal blood flow and edema were studied prospectively with perfusion-weighted MRI (PWI) and diffusion-weighted MRI in 21 ICH patients. MRI and computed tomography (CT) images were coregistered to ensure perfusion and diffusion changes were outside of the hematoma. Edema volumes were measured on T2-weighted images. Apparent diffusion coefficient (ADC) values of the edematous regions were calculated.

Results—

Mean patient age was 64.2 years (45 to 89), and median National Institutes of Health stroke scale score was 12 (3 to 24). Median time to MRI was 21 hours (4.5 to 110). Average hematoma volume on CT was 26.1 (4 to 84) mL. PWI demonstrated perihematomal relative mean transit time (rMTT) was significantly correlated with hematoma volume (
r
=0.60;
P
=0.004) but not edema volume. Perihematomal oligemia (rMTT >2 s) was present in patients with hematoma volumes of >15 mL (average rMTT 4.6±2.0 s). Perihematomal edema was present in all patients. ADC values within this region (1178±213×10
−6
mm
2
/s) were increased 29% relative to contralateral homologous regions. Increases in perihematomal ADC predicted edema volume (
r
=0.54;
P
=0.012) and this was confirmed with multivariate analysis.

Conclusions—

Acute perihematomal oligemia occurs in acute ICH but is not associated with MRI markers of ischemia and is unrelated to edema formation. Increased rates of water diffusion in the perihematomal region independently predict edema volume, suggesting the latter is plasma derived.
A Preference for Phase-Based Disparity in a Neuromorphic Implementation of the Binocular Energy Model
Authors: Tsang Eric K. C. , Shi Bertram E.
Published: June 2004

The relative depth of objects causes small shifts in the left and right retinal positions of these objects, called binocular disparity. This letter describes an electronic implementation of a single binocularly tuned complex cell based on the binocular energy model, which has been proposed to model disparity-tuned complex cells in the mammalian primary visual cortex. Our system consists of two silicon retinas representing the left and right eyes, two silicon chips containing retinotopic arrays of spiking neurons with monocular Gabor-type spatial receptive fields, and logic circuits that combine the spike outputs to compute a disparity-selective complex cell response. The tuned disparity can be adjusted electronically by introducing either position or phase shifts between the monocular receptive field profiles. Mismatch between the monocular receptive field profiles caused by transistor mismatch can degrade the relative responses of neurons tuned to different disparities. In our system, the relative responses between neurons tuned by phase encoding are better matched than neurons tuned by position encoding. Our numerical sensitivity analysis indicates that the relative responses of phase-encoded neurons that are least sensitive to the receptive field parameters vary the most in our system. We conjecture that this robustness may be one reason for the existence of phase-encoded disparity-tuned neurons in biological neural systems.
Decomposition Methods for Linear Support Vector Machines
Authors: Kao Wei-Chun , Chung Kai-Min , Sun Chia-Liang , Lin Chih-Jen
Published: June 2004

In this letter, we show that decomposition methods with alpha seeding are extremely useful for solving a sequence of linear support vector machines (SVMs) with more data than attributes. This strategy is motivated by Keerthi and Lin (2003), who proved that for an SVM with data not linearly separable, after C is large enough, the dual solutions have the same free and bounded components. We explain why a direct use of decomposition methods for linear SVMs is sometimes very slow and then analyze why alpha seeding is much more effective for linear than nonlinear SVMs. We also conduct comparisons with other methods that are efficient for linear SVMs and demonstrate the effectiveness of alpha seeding techniques in model selection.
The Role of Mary as Co-recapitulator in St Irenaeus of Lyons
Authors:   Steenberg
Published: June 2004

In this article, the author takes up the theme of Marian consideration in the thought of Irenaeus, long considered by many to have been exhaustively addressed by past scholarship. But there is yet ground to be covered: this study addresses the hitherto neglected theme of co-recapitulation as it applies to Mary in the Irenaean corpus. What to make of Irenaeus' assertions of an active, dynamic participation in the salvation process by the 'obedient virgin'? Arguing against the possibility that Irenaeus is driven primarily by aesthetic concerns, the author posits a reading of Irenaeus that finds in Mary's person an integral and essential component of a theologically coherent system of personal and social recapitulation.
NHC II,2 and the Oxyrhynchus Fragments (P.Oxy 1, 654, 655): Overlooked Evidence for a Syriac Gospel of Thomas
Authors: Perrin Nicholas
Published: June 2004

Whereas it is generally assumed that the Gospel of Thomas was first composed in Greek, here the author finds evidence, confirming his earlier published thesis, that the well-known Nag Hammadi text was first set down in Syriac. On comparing divergences between the Greek witness to Thomas (P.Oxy 1, 654, 655) and the fuller Coptic version (NHC II,2), it is argued that each of these differences can be readily attributed to the texts' final reliance on a common Aramaic source. In most instances, the hypothesized shared source may be inferred to be of either western Aramaic or Syriac character, but in some cases, the evidence points decisively toward Syriac-speaking provenance. Consequently, the investigation sheds light not only on the relationship between the two extant witnesses of Thomas, but on its dating as well.
Sallust in Julian of Aeclanum
Authors: Lössl Josef
Published: June 2004

The importance of Cicero in the debate between Augustine of Hippo and Julian of Aeclanum has been extensively studied. This includes Augustine's and Julian's use of the Catilinarian speeches in their polemics against each other. In comparison the use of Sallust, the other classical authority on Catiline, especially by Julian of Aeclanum, has been neglected. This paper intends to remedy that situation. Textual evidence may be meagre: barely two literal citations in three of the extant fragments of Julian's writings. But Julian's use of these, also compared with Jerome's and Augustine's, and the way his use of Sallust is reflected in the rest of his extant writing and thought gives the impression that he may have been far more deeply influenced by Sallust than has hitherto been thought.
Cleaning Up Our Own Backyard
Authors: Jempson Mike
Published: June 2004

Mike Jempson, a journalist for 30 years and is now director of The PressWise Trust (MediaWise), the charity that provides advice and training on media ethics issues, examines the case for statutory control and concludes: "Fear of a media backlash may have persuaded successive governments to fight shy of statutory controls, but how would the industry react if civil society groups were to devise alternative methods of holding us to account? Among those I have heard bruited in reputable quarters is publication on the internet of the assets, political affiliations and financial interests of individual journalists. Or lists of untrustworthy journalists to whom no one should speak. Others have mooted the idea of hiring hire private detectives to spy on editors to expose their infidelities, financial dealings and substance abuse. I am sure the media would denounce them as vindictive busybodies... But who knows what support such naming and shaming might win if the public at last refuses to accept journalists operating with impunity and journalism condoning unethical conduct in the pursuit of profit?"
Here is the Views-as-news
Authors: Mayes Tessa
Published: June 2004

Media commentator Mayes expresses concern over the amount of opinion now being injected into newspaper and television news reporting. "What appears to be a harmless new style to 'engage' people has altered journalistic standards - and not for the better," she writes. "Worse, perhaps, is the possibility of this variation in news values may have contributed to the erosion of trust between the news media and the public. After all why should the public rely on news reporters if they're seen only to be offering yet another opinion? The cliché used to be, 'You can't believe everything you read in the newspapers or see on TV.' Now it's in danger of becoming: 'You can't believe anything.'"
Trust Me – I’m an Ombudsman
Authors: Mayes Ian
Published: June 2004

To mark the annual conference of the Organisation of News Ombudsmen, The Guardian's readers' editor stresses the independence of his role and asks: "Why hasn't the idea moved faster and farther? After all, it has been around for almost half a century. Crises such as the Jayson Blair affair at The New York Times and that involving Andrew Gilligan at the BBC have focused minds. The New York Times, although it has been an assiduous corrector for years, had always resisted the idea of having an ombudsman. In the words of its former executive editor Joe Lelyveld, "We are the ombudsmen." It has now, post-Blair, appointed one. The BBC is also rethinking its system for responding to complaints. Alan Rusbridger, whose idea it was to introduce an ombudsman to The Guardian, keeps making the point that in the rapidly changing media environment trust is becoming more important than ever."
Are Our Utopian Energies Exhausted?
Authors: Johnson Pauline
Published: June 2004

This article starts off by giving Habermas the opportunity to defend the ‘remnants of utopianism’ in his thinking that might seem to fly in the face of grim sociological realities. He wants to cut the ground from under a fashionable scepticism about our capacity to use a description of the unrealized potentials of the present as the basis for orienting ourselves to a desired future. This is to be done by persuading us that we have been looking in the wrong place for an account of the utopian significance of modernizing achievements. The defeat of utopian energies thesis rests on a one-sided description of modernization processes that neglects their complex and ambiguous achievements and, in particular, ignores the legacy of democratic Enlightenment. Yet Habermas’s own estimation of the ambiguous legacies of cultural modernization also appears to be one-sided. The last part of the article finds that his argument with the end of utopian energies thesis rests on a narrow appreciation of the range of ways in which the potentials of cultural modernization have been described. There is, after all, a residual totalizing description of the role of the theorist in Habermas’s inability to concede the irreducible integrity of Romantic hopes for emancipated futures.
Underwater friction surfacing
Authors: Li J.Q. , Shinoda T.
Published: June 2004

Underwater friction surfacing experiments were carried out in a waterbath to clarify the effect of the surrounding medium on the characteristics of the process and the deposit. A quench hardenable martensitic stainless steel with 1%C and 17%Cr was used as the coating material and low carbon structural steel as the substrate. The mechanisms of friction surfacing have been analysed and the results show that a uniform hardness distribution and refined microstructure can be achieved in the transverse section of the deposit. As a result of the cooling effect of water, the deposition efficiency of the consumable material under water was greater than in air. Defects such as quench cracks were not observed in water owing to the reheating characteristics of the underwater friction surfacing process.
Preparation of NiOx thin films on SnO2 : F for electrochromic applications
Authors: Jiménez-González A.E. , Cambray J.G. , Gutiérrez A.A.R.
Published: June 2004

By combining the electrochemical and sol–gel deposition methods it was possible to prepare the heterojunction NiOx -SnO2 : F. High quality SnO2 : F thin films were prepared by the sol–gel technique on glass substrates. These films are very transparent in the visible region, with optical transmittance >85%, and have conductivity around 230 Ω-1 cm-1. By using electrochemical deposition it was possible to grow NiOx thin films on SnO2 : F coated glass substrates. Optical and electrical properties of the NiOx -SnO2 : F interface are detailed in the present study. Cyclic voltammetry measurements of NiOx thin films deposited on SnO2 : F show clearly the reversible movement of electrons, protons, and positive ions into the electrochromic NiOx film. With such results, the NiOx -SnO2 : F interface shows potential for application in electrochromic devices.
Self-Limiting Hardness Changes in Laser Peened 6061-T6 Aluminium
Authors: Montross C.S. , Brandt M. , Swain M.V.
Published: June 2004

Laser peening uses shock waves to modify and work harden the surface of metal components and weldments to improve mechanical properties such as fatigue and wear resistance, in particular with aluminium alloys. The literature has reported on a variety of property changes from laser peening aluminium alloys, which varied with the initial metallurgical state and laser generated shock wave pressures. This paper analyses the effect of laser peening repetitions (one and five repetitions) on hardness and elastic modulus versus depth on a 6061-T6 specimen for two laser generated shock wave pressures of 3·5 and 6 GPa. The higher shock wave pressure increased the hardness with both one and five repetitions, however, the lower shock wave pressure only increased the hardness with one repetition and not with five. The two mechanisms responsible for the self-limiting hardness changes are increases in the metal's Hugoniot elastic limit and changes in the metal's dynamic yield strength. These mechanisms limit further shock processing and surface hardness changes in the metal unless the laser generated shock wave pressure remains significantly greater than the increased Hugoniot elastic limit and dynamic yield strength.
Improvement of Intergranular Corrosion Resistance of Type 316 Stainless Steel by Laser Surface Melting
Authors: Kumar S. , Banerjee M.K.
Published: June 2004

Laser surface melting (LSM) on sensitised austenitic stainless steel with various degrees of cold work (5, 10, 15, 20, and 25%) was carried out by using a continuous wave CO2 laser with a maximum power 450 W. The stainless steel was sensitised at 898 K for 10, 20, and 50 h durations. The ASTM A262 Practice A test was used to examine the microstructures of the specimens before and after LSM, while the single loop electrochemical potentiokinetic reactivation (SL-EPR) technique was used to quantify the degree of sensitisation (DOS). A trend is noted between the level of cold work in the stainless steel and the degree of desensitisation by LSM and it is inferred that laser surface melting can be effectively used as a method to improve the intergranular corrosion resistance of austenitic stainless steel.
Low Temperature Fabrication of Sol–Gel PZT Thin Films and Structural Characterisation of C60 Precipitates Formed in PZT–C60 Sol
Authors: Miyazawa K. , Obayashi A. , Kuwabara M. , Maeda R.
Published: June 2004

Lead zirconate titanate (PZT) thin films were prepared at 400°C, in air by using PZT solutions containing C60, toluene, and acetic acid. All these additives provided well-developed perovskite PZT crystals, and the formation of pyrochlore crystals was suppressed. The 〈100〉 preferred orientation of perovskite PZT crystals was found to develop in the PZT thin films fabricated by using the solutions mixed with acetic acid. Needlelike and wirelike crystals of C60 were observed to precipitate in a PZT solution containing C60. The dielectric constant εr and the dielectric loss tan δ of a C60 doped PZT multilayer film prepared at 400°C were measured to be ∼ 200 and ∼ 3%, respectively, for a frequency range of 500–20 000 Hz. The present low temperature sol–gel processing is expected to be utilised as a method of intermediate heat treatment for the fabrication of thick multilayer PZT films for microactuators and sensors.
Short pulse irradiation of magnesium based alloys to improve surface properties
Authors: Schippman D. , Weisheit A. , Mordike B.L.
Published: June 2004

Various magnesium alloys were irradiated with an XeCl excimer laser. The surface of the irradiated areas showed a typical wavy structure caused by the expanding plasma. The resulting roughness was significantly affected by the alloying elements used. Investigations of the microstructure by SEM and TEM revealed supersaturated structures. In the case of AZ 91 an amorphous layer was produced, probably as a result of trapping of oxygen. The refinement and homogenis ation of the microstructure led to improved corrosion resistance.