bluuebunny/crossref_metadata_2025 huggingface dataset:
High Methionine and Cholesterol Diet Abolishes Endothelial Relaxation
Authors: Zulli Anthony , Widdop Robert E. , Hare David L. , Buxton Brian F. , Black M. Jane
Published: June 2003

Objective—

High plasma cholesterol or homocysteine is a risk factor for atherosclerosis. Cholesterol and methionine, the precursor of homocysteine, are rarely eaten separately. Thus, the aims of this study were to determine neointima formation, aortic reactivity, and factors involved in endothelial function in rabbits fed high dietary cholesterol, methionine, or a combination of the two for 12 weeks.

Methods and Results—

Rabbit dietary groups were randomized into the following: control (Con), 0.5% cholesterol (Chol), 1% methionine (Meth), and 1% methionine+0.5% cholesterol (MethChol). Aortic reactivity was studied by isometric tension techniques, aortic volumetric analysis was determined by stereological techniques, and immunohistochemistry was used to localize endothelial and inducible NO synthases, superoxide dismutase, macrophages, and nitrotyrosine. Atherosclerosis was present in the Chol and MethChol groups. Endothelium-dependent relaxation was virtually abolished in the MethChol group compared with control. Such decrease in relaxation was not attributable to a vascular smooth muscle cell defect or to a decrease in endothelial NO synthase or superoxide dismutase content. Macrophages and inducible NO synthase immunoreactivity were present in Chol and MetChol groups.

Conclusions—

The combination of high dietary cholesterol plus methionine virtually abolishes endothelium-dependent relaxation, underscoring the importance of multiple risk factors in the development of cardiovascular disease.
Expression of Human Hepatic Lipase in the Rabbit Model Preferentially Enhances the Clearance of Triglyceride-Enriched Versus Native High-Density Lipoprotein Apolipoprotein A-I
Authors: Rashid Shirya , Trinh Denny K. , Uffelman Kristine D. , Cohn Jeffrey S. , Rader Daniel J. , Lewis Gary F.
Published: June 2003

Background—

We have shown previously that triglyceride (TG) enrichment of HDL, as occurs in hypertriglyceridemic states, contributes to HDL lowering in humans by enhancing the clearance of HDL apolipoprotein (apo) A-I from the circulation. In the New Zealand White rabbit, an animal naturally deficient in hepatic lipase (HL), we demonstrated that TG enrichment of HDL per se is not sufficient to enhance HDL clearance in the absence of ex vivo lipolysis by HL. Here, we examined in the rabbit the interaction between in vivo HL lipolytic action and HDL TG enrichment on the subsequent metabolic clearance of HDL apoA-I.

Methods and Results—

The clearance of HDL, TG-enriched with human VLDL (12% mass TG), was compared with a simultaneously injected native rabbit HDL tracer (8% TG) 5 to 7 days after injection of recombinant (r) adenovirus expressing either the human HL or lacZ transgene (n=6 animals each). In rHL-Adv rabbits, HL activity levels were 2- to 7-fold higher (versus rlacZ-Adv controls;
P
<0.01), and there were significant (
P
<0.05) reductions in HDL TG (−18%), cholesterol (−21%), cholesteryl ester (−24%), and phospholipid (−14%). Moreover, the clearance of TG-enriched versus native HDL was significantly greater (by 50%; 0.122±0.022 versus 0.081±0.015 pools/h;
P
<0.01) in rHL-Adv rabbits but not in controls.

Conclusions—

These studies have shown that TG enrichment of HDL in the presence but not in the absence of in vivo expression of moderate levels of lipolytically active HL results in enhanced HDL clearance, demonstrating the important interaction between TG enrichment and HL action in the pathogenesis of HDL lowering in hypertriglyceridemic states.
Clopidogrel for Coronary Stenting
Authors: Gurbel Paul A. , Bliden Kevin P. , Hiatt Bonnie L. , O’Connor Christopher M.
Published: June 2003

Background—

Clopidogrel is administered to prevent stent thrombosis; however, the uniformity of platelet inhibition after treatment and the influence of pretreatment reactivity on drug response have not been described.

Methods and Results—

Platelet aggregation (5 and 20 μmol/L ADP), the activation of glycoprotein IIb/IIIa (PAC-1 antibody), and the expression of P-selectin were measured in patients undergoing elective coronary stenting (n=96) at baseline and at 2 hours, 24 hours, 5 days, and 30 days after stenting. All patients received aspirin (325 mg). Clopidogrel (300 mg) was administered in the catheterization laboratory and followed by 75 mg daily. There was marked interindividual variability in drug response as measured by all markers that showed a normal distribution. Resistance, defined as baseline aggregation (%) minus posttreatment aggregation (%) ≤10% by 5 μmol/L ADP, was present in 31% and 15% of patients at 5 and 30 days, respectively. Patients with the highest pretreatment platelet reactivity remained the most reactive at 24 hours after treatment (
P
<0.0001).

Conclusions—

Interindividual variability in the platelet inhibitory response from clopidogrel occurs in patients undergoing elective coronary stenting. Patients with high pretreatment reactivity are least protected. Alternative pharmacological strategies and the association of adverse ischemic events should be investigated in these patients.
Prevalence of Complicated Carotid Atheroma as Detected by Magnetic Resonance Direct Thrombus Imaging in Patients With Suspected Carotid Artery Stenosis and Previous Acute Cerebral Ischemia
Authors: Murphy Rachael E. , Moody Alan R. , Morgan Paul S. , Martel Anne L. , Delay G.S. , Allder Steve , MacSweeney Shane T. , Tennant William G. , Gladman John , Lowe John , Hunt Beverley J.
Published: June 2003

Background—

It is recognized that complicated plaque largely accounts for the morbidity and mortality from atherosclerosis. Ideally, investigation of symptomatic and asymptomatic patients would identify atheromatous plaques independently of stenosis. We have previously shown that a magnetic resonance direct thrombus imaging (MRDTI) technique demonstrates complicated atheroma as high signal within the carotid arterial wall. We used this technique to examine the prevalence of complicated carotid plaque in vivo in the ipsilateral arteries of recently symptomatic patients with suspected carotid artery stenosis and to compare this with their contralateral arteries and with those of healthy age- and sex-matched controls.

Methods and Results—

The carotid arteries of 120 patients with suspected severe carotid artery stenosis and previous acute cerebral ischemia were imaged using MRDTI, as were 28 control arteries. High signal was not seen in any control artery. However, there was a 60% prevalence of high signal, suggestive of complicated plaque in the patients’ ipsilateral arteries. The prevalence of high signal was significantly greater in the patients’ ipsilateral vessels compared with the contralateral, asymptomatic side (60% versus 36%, χ
2
P
<0.001), particularly for vessels of only moderate stenosis.

Conclusions—

MRDTI high signal suggestive of complicated plaque is prevalent in the ipsilateral carotid arteries of patients with carotid stenosis and recent cerebral ischemic events. MRDTI has a potential role in identifying “at risk” plaque, studying atherogenesis and the effects of plaque-modifying strategies.
Increased Levels of C-Reactive Protein After Oral Hormone Replacement Therapy May Not Be Related to an Increased Inflammatory Response
Authors: Silvestri Antonello , Gebara Otavio , Vitale Cristiana , Wajngarten Mauricio , Leonardo Filippo , Ramires Josè A.F. , Fini Massimo , Mercuro Giuseppe , Rosano Giuseppe M.C.
Published: June 2003

Background—

It has been suggested that hormone replacement therapy (HRT) in postmenopausal women is associated with an increased inflammatory response that may trigger acute cardiovascular events. This suggestion is mainly based on the finding of elevated C-reactive protein (CRP) levels after HRT. The aim of the present study was to evaluate a broad spectrum of vascular inflammation markers in 389 postmenopausal women with increased cardiovascular risk at baseline and after either 6 months of HRT (126 women) or no HRT (263 women).

Methods and Results—

Compared with baseline, CRP levels significantly increased after HRT (0.9±0.2 versus 1.6±0.4 mg/L,
P
<0.01); on the contrary, soluble intracellular adhesion molecule-1 decreased from 208±57 to 168±37 ng/mL (
P
<0.01) after HRT. Similarly, vascular cell adhesion molecule-1 decreased from 298±73 to 258±47 ng/mL (
P
<0.01), plasma E-selectin levels were reduced from 17.8±5.6 to 14.8±3.9 ng/mL (
P
<0.01), interleukin-6 levels decreased from 1.51±0.22 to 1.29±0.28 pg/mL, and s-thrombomodulin plasma levels decreased from 4.8±0.7 to 4.3±0.9 ng/mL (
P
<0.01). No significant changes in either CRP or vascular inflammatory marker were detected in women not taking HRT.

Conclusions—

The discrepancy between increased plasma levels of CRP and reduced plasma levels of all other markers of inflammation suggests that the increased CRP levels after oral HRT may be related to metabolic hepatic activation and not to an acute-phase response. HRT seems to be associated with an overall decrease in vascular inflammation.
Characterization of Complicated Carotid Plaque With Magnetic Resonance Direct Thrombus Imaging in Patients With Cerebral Ischemia
Authors: Moody Alan R. , Murphy Rachael E. , Morgan Paul S. , Martel Anne L. , Delay G.S. , Allder Steve , MacSweeney Shane T. , Tennant William G. , Gladman John , Lowe John , Hunt Beverley J.
Published: June 2003

Background—

Thromboembolic disease secondary to complicated carotid atherosclerotic plaque is a major cause of cerebral ischemia. Clinical management relies on the detection of significant (>70%) carotid stenosis. A large proportion of patients suffer irreversible cerebral ischemia as a result of lesser degrees of stenosis. Diagnostic techniques that can identify nonstenotic high-risk plaque would therefore be beneficial. High-risk plaque is defined histologically if it contains hemorrhage/thrombus. Magnetic resonance direct thrombus imaging (MRDTI) is capable of detecting methemoglobin within intraplaque hemorrhage. We assessed this as a marker of complicated plaque and compared its accuracy with histological examination of surgical endarterectomy specimens.

Methods and Results—

Sixty-three patients underwent successful MRDTI and endarterectomy with histological examination. Of these, 44 were histologically defined as complicated (type VI plaque). MRDTI demonstrated 3 false-positive and 7 false-negative results, giving a sensitivity and specificity of 84%, negative predictive value of 70%, and positive predictive value of 93%. The interobserver (κ=0.75) and intraobserver (κ=0.9) agreement for reading MRDTI scans was good.

Conclusions—

MRDTI of the carotid vessels in patients with cerebral ischemia is an accurate means of identifying histologically confirmed complicated plaque. The high contrast generated by short T
1
species within the plaque allows for ease of interpretation, making this technique highly applicable in the research and clinical setting for the investigation of carotid atherosclerotic disease.
Frame Count Reserve
Authors: Stoel Martin G. , Zijlstra Felix , Visser Cees A.
Published: June 2003

Background—

The Doppler wire–derived (relative) coronary flow velocity reserve (CVR) that is used to evaluate functional significance of a coronary stenosis is a method performed only by interventional cardiologists. An angiographic method would be useful in the diagnostic catheterization laboratory. For this purpose, we investigated the relation between TIMI frame count reserve (FCR) and CVR.

Methods and Results—

In 38 patients, (relative) FCR of left anterior descending (LAD) and left circumflex coronary artery (LCx) was calculated by using manual, synchronized contrast agent injections and compared with (relative) CVR. In addition, vessel length was measured with an intracoronary guidewire and frame count flow velocity was calculated and compared with average peak velocity. There was a strong correlation between FCR and CVR (
r
=0.62,
P
<0.001) and between relative FCR and relative CVR (
r
=0.84,
P
<0.001). The LAD was significantly longer than the LCx (mean, 14.3±1.6 cm versus 11.4±1.8 cm,
P
<0.001), and, therefore, TIMI frame count of LAD was significantly higher than of LCx (mean basal 32.5±15.1 versus 23.6±9.1 and hyperemic 12.1±6.6 versus 8.7±3.2, both
P
<0.02). However, all flow velocity measurements and estimations of volume flow were not different for LAD compared with LCx. There were also no differences between mean FCR and CVR of LAD or LCx, of both vessels compared with each other and between mean relative FCR and relative CVR.

Conclusion—

The (relative) frame count reserve can be used to estimate (relative) coronary flow velocity reserve.
Combined Epicardial and Endocardial Electroanatomic Mapping in a Porcine Model of Healed Myocardial Infarction
Authors: Reddy Vivek Y. , Wrobleski David , Houghtaling Christopher , Josephson Mark E. , Ruskin Jeremy N.
Published: June 2003

Background—

Substrate mapping of post–myocardial infarction ventricular tachycardia involves electroanatomic delineation of scarred tissue on the basis of electrogram characteristics during sinus rhythm. A percutaneous transthoracic technique was recently described that allows catheter mapping of the epicardial surface of the heart. This study sought to determine whether the epicardial extent of a myocardial infarct could be defined during sinus rhythm.

Methods and Results—

In a porcine model of healed anterior wall myocardial infarction (n=13 animals), detailed in vivo left ventricular endocardial and ventricular epicardial electroanatomic mapping was performed. Catheter access to the pericardial space was achieved by subxyphoid puncture under fluoroscopic guidance. Bipolar electrogram amplitude and duration characteristics of normal tissue were established on the basis of in vivo epicardial mapping data in 8 additional normal animals. With the use of these criteria, radiofrequency lesions (4 to 11 per animal) were placed along the endocardial and epicardial scar borders as defined by the electroanatomic map. The area of epicardial scar defined by abnormal bipolar voltage correlated well with the dimensions measured on pathological examination. The size and location also correlated well with the scar dimensions defined by electrogram duration criteria. Late potentials were noted in the border zones of both surfaces of the scar. During pathological examination, the radiofrequency lesions were situated at the borders of the epicardial scar.

Conclusions—

A 3-dimensional construct of the infarcted myocardium can be rendered by combined epicardial and endocardial electroanatomic mapping. This experimental protocol is propaedeutic to future clinical studies incorporating endocardial and epicardial substrate mapping into catheter ablation strategies to treat post–myocardial infarction ventricular tachycardia.
Hearts From Rodents Exposed to Intermittent Hypoxia or Erythropoietin Are Protected Against Ischemia-Reperfusion Injury
Authors: Cai Zheqing , Manalo Dominador J. , Wei Guo , Rodriguez E. Rene , Fox-Talbot Karen , Lu Huasheng , Zweier Jay L. , Semenza Gregg L.
Published: June 2003

Background—

Preconditioning phenomena provide evidence for adaptive responses to ischemia that have important implications for treatment/prevention of myocardial infarction. Hypoxia-inducible factor 1 (HIF-1) mediates adaptive transcriptional responses to hypoxia/ischemia.

Methods and Results—

Exposure of wild-type mice to intermittent hypoxia resulted in protection of isolated hearts against ischemia-reperfusion injury 24 hours later. Cardiac protection induced by intermittent hypoxia was lost in
Hif1a

+/
−

mice heterozygous for a knockout allele at the locus encoding HIF-1α. Erythropoietin (EPO) mRNA expression was induced in kidneys of wild-type mice subjected to intermittent hypoxia, resulting in increased plasma EPO levels. EPO mRNA expression was not induced in
Hif1a

+/
−

mice. EPO administration to rats increased functional recovery and decreased apoptosis in isolated hearts subjected to ischemia-reperfusion 24 hours later.

Conclusions—

Hearts isolated from rodents subjected to intermittent hypoxia or EPO administration are protected against postischemic injury. Cardiac protection induced by intermittent hypoxia is critically dependent on
Hif1a
gene dosage. Our data suggest that additional studies to evaluate therapeutic applications of EPO administration are warranted.
Ca
2+
Scraps
Authors: Shannon Thomas R. , Guo Tao , Bers Donald M.
Published: June 2003

Free [Ca
2+
] inside the sarcoplasmic reticulum ([Ca
2+
]
SR
) is difficult to measure yet critically important in controlling many cellular systems. In cardiac myocytes, [Ca
2+
]
SR
regulates cardiac contractility. We directly measure [Ca
2+
]
SR
in intact cardiac myocytes dynamically and quantitatively during beats, with high spatial resolution. Diastolic [Ca
2+
]
SR
(1 to 1.5 mmol/L) is only partially depleted (24% to 63%) during contraction. There is little temporal delay in the decline in [Ca
2+
]
SR
at release junctions and between junctions, indicating rapid internal diffusion. The incomplete local Ca
2+
release shows that the inherently positive feedback of Ca
2+
-induced Ca
2+
release terminates, despite a large residual driving force. These findings place stringent novel constraints on how excitation-contraction coupling works in heart and also reveal a Ca
2+
store reserve that could in principle be a therapeutic target to enhance cardiac function in heart failure.
Homocellular Conduction Along Endothelium and Smooth Muscle of Arterioles in Hamster Cheek Pouch
Authors: Budel Stéphane , Bartlett Iain S. , Segal Steven S.
Published: June 2003

We investigated roles for homocellular (endothelium or smooth muscle) and heterocellular (myoendothelial) conduction pathways along hamster cheek pouch arterioles in vivo (n=64; diameter, 33±1 μm). Endothelium-dependent and -independent vasoactive agents were delivered from micropipettes (0.5 or 1 second pulse) onto an arteriole while observing diameter changes at defined distances along the vessel. Acetylcholine (ACh) produced maximal diameter (63±1 μm) locally and vasodilation conducted rapidly (≈10 μm response at 2 mm, <1 second). Responses to bradykinin (BK) were similar, whereas sodium nitroprusside produced maximal dilation locally without conduction. KCl evoked biphasic conduction of vasoconstriction and vasodilation, whereas phenylephrine (PE) produced conducted vasoconstriction. Disrupting the integrity of endothelium as a conduction pathway using focal light-dye treatment (LDT) abolished conducted vasodilation to BK and to KCl but not to ACh. Disruption of smooth muscle integrity with LDT abolished conducted vasoconstriction with no effect on conducted vasodilation. After LDT of respective cell layers at sites 1 mm apart, vasodilation to ACh conducted past disrupted smooth muscle or disrupted endothelium, but not beyond both sites in series. The loss of conduction after selective LDT indicates a lack of effective myoendothelial coupling along the arteriolar wall. During NO synthase inhibition (L-NA, 100 μmol/L), conducted vasodilation was abolished to BK and to KCl yet remained intact to ACh. However, after LDT of smooth muscle, L-NA inhibited conduction to ACh by 60%. Thus, conduction of vasodilation entails a wave of NO release along arteriolar endothelium that is masked when smooth muscle provides a parallel conduction pathway.
Different Expression Patterns of Bcl-2, Bcl-xl, and Bax Proteins After Sublethal Forebrain Ischemia in C57Black/Crj6 Mouse Striatum
Authors: Wu Chaoran , Fujihara Hideyoshi , Yao Jian , Qi Sihua , Li Huiping , Shimoji Koki , Baba Hiroshi
Published: June 2003

Background and Purpose—

Ischemic injury in neurons can be strongly reduced by a preceding sublethal ischemic episode, of which the mechanism is poorly understood. Although changes in the expression of apoptosis-related proteins (Bcl-2, Bcl-xl, and Bax) have been considered to be crucially important in ischemic injury, the roles these proteins play in ischemic preconditioning induced by sublethal forebrain ischemia have not been elucidated. Therefore, we investigated the transcription and expression of Bcl-2, Bcl-xl, and Bax in striatum of mice subjected to sublethal forebrain ischemia and lethal ischemia, with or without ischemic preconditioning.

Methods—

Sublethal forebrain ischemia was induced in C57Black/Crj6 (C57BL/6) mice by 6 minutes of bilateral common carotid artery occlusion. The transcription and expression of Bcl-2 family genes were detected by reverse transcription–polymerase chain reaction, Western blot, and immunofluorescent staining.

Results—

No detectable neuronal loss was induced in striatum by 6 minutes of bilateral common carotid artery occlusion. Transcription and expression of Bcl-2 and Bcl-xl were increased after sublethal forebrain ischemia, which attenuated the DNA fragmentation induced by lethal ischemia. The transcription and expression of Bax remained unchanged.

Conclusions—

Upregulation of Bcl-2 and Bcl-xl but not Bax may have a role in protective ischemic preconditioning. This result indicates a potential strategy for further ischemic neuronal injury therapies.
Rapid Perfusion Abnormality Estimation in Acute Stroke With Temporal Correlation Analysis
Authors: Lee Yueh Z. , Lee Jin-Moo , Vo Katie , Hsu Chung Y. , Lin Weili
Published: June 2003

Background and Purpose—

Determination of the presence or absence of ischemic penumbra through diffusion-perfusion mismatch requires rapid delineation of both abnormalities. Although singular value decomposition–based perfusion parameter estimation has offered valuable insights into the underlying cerebral hemodynamics, the associated postprocessing procedures have limited its widespread use. We explored the utility of a simple technique to define perfusion abnormality in acute stroke patients.

Methods—

Twenty acute stroke patients were studied. The MR dynamic contrast approach was used to obtain cerebral blood flow, cerebral blood volume, and mean transit time (MTT). Temporal correlation was used to correlate 4 reference functions—an arterial input function (AIF), a normal tissue function, a lesion function, and a venous output function—with dynamic contrast MR images, and correlation coefficients (CCs) were calculated pixel by pixel. In addition, chronic-state T2-weighted images were coregistered onto the images acquired acutely for assessing the sensitivity and specificity of CC-defined lesion.

Results—

Statistically significant differences in cerebral blood flow and MTT were found between CC-defined normal and abnormal tissues with all 4 reference functions used. When the final infarct volume was used as the gold standard, a similar sensitivity between MTT (78%) and AIF (76%) CC-defined lesion was obtained, whereas the specificity was higher for AIF (61%) than that obtained with MTT-defined lesion (52%).

Conclusions—

We explored CC maps as a simpler alternative of estimating perfusion abnormality, and results demonstrated the potential clinical utility of a correlation-based technique for estimating brain perfusion status.
Dynamic Pressure–Flow Velocity Relationships in the Human Cerebral Circulation
Authors: Aaslid Rune , Lash Stephanie R. , Bardy Gust H. , Gild William H. , Newell David W.
Published: June 2003

Background and Purpose—

The pressure–flow velocity relationship in the cerebral circulation is characterized by the critical closing pressure (CCP), which is the pressure at which flow ceases, and the linear slope of a plot between pressure and flow velocity. It has been suggested, but not validated, that CCP can be determined from arterial blood pressure (ABP) and transcranial Doppler (TCD) recordings during the cardiac cycle. We studied a group of patients in whom ventricular fibrillation (VF) was induced. The time interval before defibrillation enabled calculation of CCP from data in which flow approached zero. These estimates were compared with values calculated before and after fibrillation and during regular heartbeats.

Methods—

TCD velocities and ABP in the radial artery were recorded before, during, and after 28 episodes of VF in 13 patients. CCPs were calculated by 3 different methods: (1) linear extrapolation from data during VF (gold standard); (2) linear extrapolation from normal heartbeat data; and (3) first harmonic Fourier filtering of normal heartbeat data.

Results—

The CCP during VF calculated from long diastoles was 32.9±11 mm Hg (mean±SD). The regular heartbeat estimate was 6.0±4.3 mm Hg lower (
P
<0.05). The CCP estimate with the use of a Fourier filter was 1.4±3.9 mm Hg (
P
=NS) lower than during VF. During hyperemia after defibrillation, the CCP decreased by 13.3 mm Hg, while velocity increased by 63%. The decrease in CCP could explain half of the increase in flow velocity during hyperemia.

Conclusions—

CCP can be accurately estimated from regular heartbeat data and is an important factor in regulation of the cerebral circulation.
Pentanucleotide TTTTA Repeat Polymorphism of Apolipoprotein(a) Gene and Plasma Lipoprotein(a) Are Associated With Ischemic and Hemorrhagic Stroke in Chinese
Authors: Sun Li , Li Zhaohui , Zhang Hongye , Ma Aiqun , Liao Yuhua , Wang Daowen , Zhao Bingrang , Zhu Zhiming , Zhao Jizong , Zhang Zhen , Wang Wei , Hui Rutai
Published: June 2003

Background and Purpose—

It is still inconclusive whether high plasma lipoprotein(a) [Lp(a)] level is a risk factor for stroke. Small sample size and different ethnic groups and methodologies might be contributors to the conflicts in study results. The purpose of the present study was to investigate the association between plasma Lp(a) levels, pentanucleotide TTTTA repeat (PNTR) polymorphism of the apolipoprotein(a) [apo(a)] gene, and Chinese stroke in a case-control study.

Methods—

We recruited 1825 cases with stroke (44.3% cerebral atherothrombosis, 28.3% lacunar infarction, and 27.3% intracerebral hemorrhage) and 1817 controls from 7 centers in China. Lp(a) concentrations were quantified by enzyme-linked immunosorbent assay. The PNTR polymorphism of the apo(a) gene was determined by polymerase chain reaction–polyacrylamide gel electrophoresis. Conditional multivariate logistic regression analysis was used to identify independent risk factors for stroke and its subtypes.

Results—

Lp(a) levels were significantly higher in cases than in controls (median, 28.5 versus 23.1 mg/dL;
P
<0.001), leading to a 1.97-fold (95% CI, 1.64 to 2.37) increase in risk for overall stroke, 2.0-fold (95% CI, 1.59 to 2.52) increase for atherothrombotic type, 2.05-fold increase (95% CI, 1.59 to 2.63) for lacunar type, and 1.64-fold increase (95% CI, 1.21 to 2.21) for hemorrhagic type. The number of PNTR negatively correlated with Lp(a) levels. Low-number repeats (sum of both alleles <16) of apo(a) PNTR were associated with both atherothrombotic stroke (odds ratio, 1.41; 95% CI, 1.04 to 1.91) and hemorrhagic stroke (odds ratio, 1.62; 95% CI, 1.09 to 2.37).

Conclusions—

Our results indicate for the first time that low numbers of apo(a) PNTR and plasma Lp(a) levels are independently associated with both ischemic and hemorrhagic stroke in Chinese.
Democracy's Performance
Authors: McKenzie Jon
Published: June 2003

McKenzie asks, “If the ancient Greeks invented democracy in the form of the city-state, and colonial North Americans reinvented it in the nation-state, what democratic forms might the world create in the age of global performance?” He explores this question in relation to the thought of Nietzsche and Marcuse—and in terms of “dissatisfied democrats”: people who strongly believe in democracy but are unhappy with its particular embodiments. Could it be that democracy is an inherently incomplete project, one that is always “to come,” always being invented, always being tested and contested, always being asked to perform?

The Electronic Disturbance Theater demonstrates how the Internet can be used to facilitate social and political engagement and protest. Dubbed “virtual Zapatistas” because of its strong support for the liberation movement in Mexico and throughout Latin America, EDT's actions combine the political struggle for indigenous self-determination with a critique of neoliberalism aka globalization. In the articles and interview that follow, EDT's origins, development, and ongoing actions are examined. You are invited to participate.
A Monte Carlo Comparison of Item and Person Statistics Based on Item Response Theory versus Classical Test Theory
Authors: Macdonald Paul , Paunonen Sampo V.
Published: June 2003

Despite the well-known theoretical advantages of item response theory (IRT) over classical test theory (CTT), research examining their empirical properties has failed to reveal consistent, demonstrable differences. Using Monte Carlo techniques with simulated test data, this study examined the behavior of item and person statistics obtained from these two measurement frameworks. The findings suggest IRT- and CTT-based item difficulty and person ability estimates were highly comparable, invariant, and accurate in the test conditions simulated. However, whereas item discrimination estimates based on IRT were accurate across most of the experimental conditions, CTT-based item discrimination estimates proved accurate under some conditions only. Implications of the results of this study for psychometric item analysis and item selection are discussed.
Bias-Corrected Estimator of Factor Loadings in Bayesian Factor Analysis
Authors: Hayashi Kentaro , Sen Pranab K.
Published: June 2003

A Bayesian factor analysis model is implemented to formulate estimators of the hyperparameters. Motivated by a simulation study that revealed significant bias in the Bayes estimates of factor loadings, new bias-corrected estimators of factor loadings in the Bayesian factor analysis are proposed and their properties studied; a simulation study reveals a more favorable picture.
The Unseen Power Loss: Stemming the Flow
Authors: Gillett Raphael
Published: June 2003

The widespread practice of substituting an empirical estimate of effect size in the standard sample size formula causes the average power of studies to fall below the nominal level,oftenby a considerable margin. Ordinarily concealed from view in an individual experiment, the power loss becomes visible when studies are examined collectively. To help researchers avoid the power deficit, the expected-power method of sample size determination is described. When information from an earlier study is available, it is recommended that researchers should base sample size calculations on the expected-power formula instead of the traditional power formula.
A Reliability Generalization Study of the Geriatric Depression Scale
Authors: Kieffer Kevin M. , Reese Robert J.
Published: June 2003

Depression has proven to be a serious illness in older adults that often goes untreated because it is frequently misdiagnosed or is confused with other symptom patterns. One instrument that has been consistently cited in the literature as an effective indicator of depression in older adults is the Geriatric Depression Scale (GDS). The present study provided a reliability generalization (RG) study of the GDS in an effort to further distill psychometric properties of the scores generated by this measure. RG, a relatively new meta-analytic reliability procedure, was used to (a) identify the typical reliability of GDS scores across studies and (b) examine sources of measurement error across studies. Results from this investigation of 338 previously published research studies indicated that the average score reliability across studies was .8482 ( SD = .0870) and that the number of items on the scale, scale SD, sample size, and participant population were the most important predictors of score reliability on this measure. Implications for the use of the GDS are offered.
Confirmatory Factor Analysis of the Cancer Locus of Control Scale
Authors: Henderson Jessica W. , Donatelle Rebecca J. , Acock Alan C.
Published: June 2003

Perceptions of control after a cancer diagnosis may have psychological and physical health significance. The control constructs are critical components of the theory of cognitive adaptation. The Cancer Locus of Control scale reflected these theoretical components and was administered to 543 women with a history of breast cancer. Confirmatory factor analysis was conducted to assess the measurement factor structure of the Cancer Locus of Control. The results supported a three-factor model of the Cancer Locus of Control scale. Mean scores of beliefs in all three dimensions indicated generally high confidence in cancer control. It was concluded that use of this Cancer Locus of Control scale can provide adequate assessment of the three distinct control dimensions.
The Teachers’ Reactions to School Violence Scale: Psychometric Properties and Scale Development
Authors: Ting Laura , Sanders Sara , Smith Pamela L.
Published: June 2003

In response to the concern with and severity of school violence and the limited research on teachers’responses to these events, the Teachers’Reactions to School Violence Scale (TRSV) was developed. The TRSV is a self-report scale with 35 items measuring teachers’ reactions in relation to an incident of school violence. The convenience sample consisted of 143 middle and high school teachers. A principal components analysis yielded six components: Intrusion, Perceived Safety With Students, Avoidance of Students/Situations, Trust of Students, Environmental Safety, and Feelings of Relief. The six components accounted for 67% of the total variance, and subscale reliabilities ranged from .60 to .95. Convergent and discriminant validity was assessed through validation of the TRSV against the Impact of Events Scale. In addition, a comparison of teachers in perceived high-violence schools with teachers in perceived low-violence schools was used to examine criterion-related validity.
Reliability, Structure, and Correlates of Learning and Study Strategies Inventory Scores
Authors: Melancon Janet G.
Published: June 2003

The Learning and Study Strategies Inventory (LASSI) is used in hundreds of universities and high schools each year. This study investigated the reliability, structure, and criterion-related validity of LASSI scores. Data were provided by 502 university students. Results suggest that the LASSI may not measure the postulated 10 scales typically used to report results.
Measuring Interest in Reading Social Studies Materials
Authors: Ataya Rosemarie L. , Kulikowich Jonna M.
Published: June 2003

The development of the Social Studies Interest Inventory–Interest in Reading Materials is described in this study. Two hundred sixty-three middle school students and 320 high school students enrolled in an urban school district in a New England state participated in the study. The 15-item inventory used a 5-point Likert scale to assess student interest in reading materials related to the discipline of social studies. Exploratory factor analysis (EFA) of student scores yielded three dimensions of interest for social studies reading materials: (a) Textbook Materials, (b) Creative Materials, and (c) News Materials. Confirmatory factor analysis (CFA) supported the derived factor structure. By comparing the three factor scores, it is determined that students reported significantly more interest in reading Creative Materials than they did Textbook or News Materials. Based on these results, suggestions are offered for future research and practice.
Group Data on High School Grade Point Averages and Scores on Academic Aptitude Tests As Predictors of Institutional Graduation Rates
Authors: Stumpf Heinrich , Stanley Julian C.
Published: June 2003

For every 4-year college in the United States listed in the 1998 College Handbook of the College Board, the percentages of students graduating within 6 years of entering and of students having high school grade point averages (GPAs) of at least 3.00 were recorded. The authors also obtained the College Board Scholastic Assessment Test I (SAT I) Verbal and Math and the American College Test (ACT) scores at the 25th and 75th percentiles of the distributions of scores of the enrolled freshmen. The SAT I Verbal and Math and the ACT scores at the 25th and 75th percentiles proved to be good predictors of the percentage of students graduating from the same institution that admitted them as freshmen ( rs ranging from .62 to .73), as did the percentage of freshmen having high school GPAs of 3.00 or higher ( r = .49). The correlations of the group percentages and means with the criterion were considerably higher than the predictive-validity coefficients of the SAT I and ACT scores for individual graduation as reported in the literature.
Performance Differences According to Test Mode and Computer Familiarity on a Practice Graduate Record Exam
Authors: Goldberg Amie L. , Pedulla Joseph J.
Published: June 2003

Ideally, test performance is unrelated to the mode in which the test is administered. This study investigated the relationships between test mode (paper and pencil vs. computerized with editorial control and computerized without editorial control) and computer familiarity (lower, moderate, and higher) with test performance on the Graduate Record Exam (GRE). The GRE was administered to 222 undergraduates stratified by gender and randomly assigned to the three test mode groups. With self-reported grade point average as a covariate in a MANCOVA, the authors found that examinees in the paper-and-pencil group outperformed the computerized-without-editorial-control group on all subtests. The computerized-with-editorial-control group outperformed the computerized-without-editorial-control group on the Analytical subtest only. The authors also found a significant main effect for computer familiarity on the Analytical and Quantitative subtests. A significant interaction between computer familiarity and test mode on the Quantitative subtest confounded the main effect for that subtest. The subtests were dramatically more speeded in the computerized forms. The results emphasize the importance of evaluating time constraints when converting exams from paper-and-pencil to computer-delivery mode.
Enzymatically catalyzed disulfide exchange is required for platelet adhesion to collagen via integrin α2β1
Authors: Lahav Judith , Wijnen Eveline M. , Hess Oded , Hamaia Samir W. , Griffiths Delia , Makris Michael , Knight C. Graham , Essex David W. , Farndale Richard W.
Published: June 2003

Integrin α2β1 is the principal adhesive receptor for collagen but platelets also adhere through glycoprotein VI (GPVI). Integrin αIIbβ3 may augment platelet adhesion. We have shown that disulfide exchange is necessary for platelet adhesion to fibrinogen, fibronectin, and collagen. However 2 questions remained: (1) Can activated αIIbβ3 explain the observed role of disulfide exchange in adhesion to collagen, or is this role common to other integrins? (2) Is disulfide dependence specific to the integrin receptors or shared with GPVI? To discriminate adhesive functions of α2β1 from those of αIIbβ3 we used Glanzmann platelets and αIIbβ3-specific antibodies applied to normal platelets. To resolve adhesive events mediated by α2β1 from those of GPVI we used synthetic peptides specific to each receptor. We addressed direct integrin ligation using purified α2β1 and recombinant I domain. We observed the following: adhesion to the α2β1-specific peptide was disulfide-exchange dependent and protein disulfide isomerase (PDI) mediated; membrane-impermeant thiol blockers inhibited α2β1, but not GPVI mediated, adhesion; direct blockade of PDI revealed that it is involved in adhesion through α2β1 but not GPVI; and purified α2β1, but not recombinant I domain, depended on free thiols for ligation. These data suggest that the enzymatically catalyzed adhesion-associated reorganization of disulfide bonds is common to members of the integrin family and specific to this family.
Leukemia in twins: lessons in natural history
Authors: Greaves Mel F. , Maia Ana Teresa , Wiemels Joseph L. , Ford Anthony M.
Published: June 2003

Identical infant twins with concordant leukemia were first described in 1882, and since that time many such pairs of infants and older children have been described. It has long been recognized that this situation offers a unique opportunity to identify aspects of the developmental timing, natural history, and molecular genetics of pediatric leukemia in general. We reviewed both the older literature and more recent molecular biologic studies that have uncovered the basis of concordance of leukemia. Molecular markers of clonality, including unique, genomic fusion gene sequences, have provided unequivocal evidence that twin pairs of leukemia have a common clonal origin. The only plausible basis for this, first suggested more than 40 years ago, is that following initiation of leukemia in one twin fetus, clonal progeny spread to the co-twin via vascular anastomoses within a single, monochorionic placenta. This explanation has been endorsed by the identification of clonotypic gene fusion sequences in archived neonatal blood spots of individuals who subsequently developed leukemia. These analyses of twin leukemias have thrown considerable light on the natural history of disease. They reveal a frequent prenatal origin and an early or initiating role for chromosome translocations. Further, they provide evidence for a variable and often protracted latency and the need, in childhood acute lymphoblastic leukemia (ALL)/acute myeloblastic leukemia (AML), for further postnatal exposures and/or genetic events to produce clinical disease. We argue that these insights provide a very useful framework for attempts to understand etiologic mechanisms. (Blood. 2003;102:2321-2333)
Antitumor effect of donor marrow graft rejection induced by recipient leukocyte infusions in mixed chimeras prepared with nonmyeloablative conditioning: critical role for recipient-derived IFN-γ
Authors: Rubio Marie-Therese , Kim Yong-Mi , Sachs Teviah , Mapara Markus , Zhao Guiling , Sykes Megan
Published: June 2003

Some patients lose chimerism following nonmyeloablative hematopoietic cell transplantation (HCT), yet, surprisingly, enjoy sustained tumor remissions. We hypothesized that host-versus-graft (HVG) alloresponses might induce antitumor effects against recipient tumors. We explored this question in mice by administering recipient leukocyte infusions (RLIs) to mixed chimeras established with nonmyeloablative conditioning. Mixed chimeras were prepared in the B10.A (H2a)→B6 (H2b) strain combination using depleting anti–T-cell monoclonal antibodies (mAbs), cyclophosphamide, and thymic irradiation. B6 myeloid leukemia cells (MMB3.19) were administered 7 days following donor lymphocyte infusion (DLI) or RLI on day 35. Conversion to full donor chimerism occurred without graft-versus-hostdisease (GVHD) following DLI, whereas RLI led to loss of chimerism. Both RLI and DLI significantly delayed tumor mortality. In another strain combination (B10.BR [H2k]→BALB/c [H2d]), RLI-induced or spontaneous loss of chimerism was associated with antitumor effects against the host-type B-cell lymphoma A20. HCT was essential for the antitumor effect of RLI. RLI induced elevated serum interferon-γ (IFN-γ) levels, and recipient-derived IFN-γ was critical for their antitumor effects. Thus, HVG reactions (spontaneous or induced by RLI) mediate antitumor effects against hematologic malignancies via a recipient-derived IFN-γ–mediated mechanism. A novel approach to achieving anti-tumor effects without the risk of GVHD is suggested.
Localization of BCR-ABL to F-actin regulates cell adhesion but does not attenuate CML development
Authors: Wertheim Jason A. , Perera Samanthi A. , Hammer Daniel A. , Ren Ruibao , Boettiger David , Pear Warren S.
Published: June 2003

We have previously found that P210BCR-ABL increases the adhesion of hematopoietic cell lines to fibronectin by a mechanism that is independent of tyrosine kinase activity. To investigate the pathway(s) by which P210BCR-ABL influences cell adhesion, we used a quantitative cell adhesion device that can discern small changes in cell adhesion to assay P210BCR-ABL with mutations in several critical domains. We expressed P210BCR-ABL mutants in 32D myeloblast cells and found that binding to fibronectin is mediated primarily by the α5β1 integrin. We performed a structure/function analysis to map domains important for cell adhesion. Increased adhesion was mediated by 3 domains: (1) the N-terminal coiled-coil domain that facilitates oligomerization and F-actin localization; (2) bcr sequences between aa 163 to 210; and (3) F-actin localization through the C-terminal actin-binding domain of c-abl. We compared our adhesion results with the ability of these mutants to cause a chronic myelogenous leukemia (CML)–like disease in a murine bone marrow transplantation assay and found that adhesion to fibronectin did not correlate with the ability of these mutants to cause CML. Together, our results suggest that F-actin localization may play a pivotal role in modulating adhesion but that it is dispensable for the development of CML.
Most lymphoid organ dendritic cell types are phenotypically and functionally immature
Authors: Wilson Nicholas S. , El-Sukkari Dima , Belz Gabrielle T. , Smith Christopher M. , Steptoe Raymond J. , Heath William R. , Shortman Ken , Villadangos José A.
Published: June 2003

Dendritic cells (DCs) have been thought to follow a life history, typified by Langerhans cells (LCs), with 2 major developmental stages: an immature stage that captures antigens in the periphery and a mature stage that presents those antigens in the lymphoid organs. However, a systematic assessment of the maturity of lymphoid organ DCs has been lacking. We have analyzed the maturity of the DC types found in the steady state in the spleen, lymph nodes (LNs), and thymus. The DCs that migrate into the iliac, mesenteric, mediastinal, or subcutaneous LNs from peripheral tissues were mature and therefore could not process and present newly encountered antigens. However, all the other DC types were phenotypically and functionally immature: they expressed low levels of surface major histocompatibility complex class II (MHC II) and CD86, accumulated MHC II in their endosomes, and could present newly encountered antigens. These immature DCs could be induced to mature by culture in vitro or by inoculation of inflammatory stimuli in vivo. Therefore, the lymphoid organs contain a large cohort of immature DCs, most likely for the maintenance of peripheral tolerance, which can respond to infections reaching those organs and mature in situ.
Analysis of intracellular storage and regulated secretion of 3 von Willebrand disease–causing variants of von Willebrand factor
Authors: Michaux Grégoire , Hewlett Lindsay J. , Messenger Sarah L. , Goodeve Anne C. , Peake Ian R. , Daly Martina E. , Cutler Daniel F.
Published: June 2003

The rapid exocytosis of von Willebrand factor (VWF) in response to vascular injury can be attributed to the fact that VWF is stored in the Weibel-Palade bodies (WPBs) of endothelial cells. We describe a system for examining the ability of VWF to drive both the formation of a storage compartment and the function of that compartment with respect to regulated secretion. Transient transfection of HEK293 cells with wild-type human VWF cDNA leads to the formation of numerous elongated organelles that resemble WPBs. These “pseudo-WPBs” exhibit the internal structure, as well as the ability to recruit membrane proteins including P-selectin, of bona fide WPBs. Finally, VWF was efficiently secreted upon stimulation by phorbol ester. We used this system to examine 3 VWF mutations leading to von Willebrand disease that affect VWF multimerization and constitutive secretion. Surprisingly we find that all 3 mutants can, to some extent, make pseudo-WPBs that recruit appropriate membrane proteins and that are responsive to secretagogues. The most striking defects are a delay in formation and a reduction in the length and number of pseudo-WPBs in proportion to the clinical severity of the mutation. Studies of pseudo-WPB formation in this system thus yield insights into the structure-function relationships underpinning the ability of VWF to form functional WPBs. (Blood. 2003;102:2452-2458)