bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher Usual Dietary Intake of Phytoestrogens Is Associated With Lower Aortic Stiffness in Postmenopausal Women
Authors: van der Schouw Yvonne T. , Pijpe Anouk , Lebrun Corinne E.I. , Bots Michiel L. , Peeters Petra H.M. , van Staveren Wija A. , Lamberts Steven W.J. , Grobbee Diederick E.
Published: October 2002

Objective—

Phytoestrogens have been postulated to protect against cardiovascular diseases, but few studies have focused on the effect of Western dietary phytoestrogen intake.

Methods and Results—

Four hundred three women with natural menopause either between 1987 and 1989 or between 1969 and 1979 were selected from the baseline data of the PROSPECT study (n=17 395). Isoflavone and lignan intake was calculated from a food-frequency questionnaire. Aortic stiffness was noninvasively assessed by pulse-wave velocity measurement of the aorta. Linear regression analysis was used. After adjustment for age, body mass index, smoking, physical activity, mean arterial pressure, follow-up time, energy intake, dietary fiber intake, glucose, and high density lipoprotein cholesterol, increasing dietary isoflavone intake was associated with decreased aortic stiffness: −0.51 m/s (95% CI −1.00 to −0.03, fourth versus first quartile,
P
for trend=0.07). Increasing dietary intake of lignans was also associated with decreased aortic pulse-wave velocity: −0.42 m/s (95% CI −0.93 to 0.11, fourth versus first quartile,
P
for trend=0.06). Results were most pronounced in older women: for isoflavones, −0.94 m/s (95% CI −1.65 to −0.22,
P
for trend=0.02), and for lignans, −0.80 m/s (95% CI −1.85 to −0.05), fourth versus first quartile.

Conclusions—

The results of our study support the view that phytoestrogens have a protective effect on the risk of atherosclerosis and arterial degeneration through an effect on arterial walls, especially among older women.
Successful Cardiopulmonary Resuscitation After Cardiac Arrest as a “Sepsis-Like” Syndrome
Authors: Adrie Christophe , Adib-Conquy Minou , Laurent Ivan , Monchi Mehran , Vinsonneau Christophe , Fitting Catherine , Fraisse François , Dinh-Xuan A. Tuan , Carli Pierre , Spaulding Christian , Dhainaut Jean-François , Cavaillon Jean-Marc
Published: October 2002

Background

—

We investigated the immunoinflammatory profile of patients successfully resuscitated after cardiac arrest, representing a model of whole-body ischemia/reperfusion syndrome.

Methods and Results

—

Plasma cytokine, endotoxin, and ex vivo cytokine production in whole-blood assays was assessed in 61, 35, and 11 patients, respectively. On admission, high levels of plasma interleukin (IL)-6, IL-8, IL-10, and soluble tumor necrosis factor (TNF) receptor type II could discriminate between survivors and nonsurvivors. Among nonsurvivors, the initial need for a vasopressor agent was associated with higher levels of IL-1 receptor antagonist, IL-10, and IL-6 on day 1. Plasma endotoxin was detected in 46% of the analyzed patients within the 2 first days. Endotoxin-induced TNF and IL-6 productions were dramatically impaired in these patients compared with healthy control subjects, whereas an unaltered production was observed with heat-killed
Staphylococcus aureus
. In contrast, IL-1 receptor antagonist productions were enhanced in these patients compared with healthy control subjects. The productions of T-cell–derived IL-10 and interferon-γ were also impaired in these patients. Finally, using in vitro plasma exchange between healthy control subjects and patients, we demonstrated that the endotoxin-dependent hyporeactivity was an intrinsic property of patients’ leukocytes and that an immunosuppressive activity was also present in their plasma.

Conclusions

—

Altogether, the high levels of circulating cytokines, the presence of endotoxin in plasma, and the dysregulated production of cytokines found in these patients recall the immunological profile found in patients with sepsis.
Fibroblast Growth Factor Receptor-1 Signaling Induces Osteopontin Expression and Vascular Smooth Muscle Cell–Dependent Adventitial Fibroblast Migration In Vitro
Authors: Li Guohong , Oparil Suzanne , Kelpke Stacey S. , Chen Yiu-Fai , Thompson John A.
Published: October 2002

Background—

Increased expression of osteopontin (OPN), fibroblast growth factors (FGFs), and their type-1 receptor (FGFR-1) is associated with neointima formation and atherosclerosis. This study tested the hypothesis that ligand activation of FGFR-1 stimulates OPN expression in rat aortic smooth muscle cells (RASMCs), explored the signaling pathway involved, and assessed the functional consequences of activating this pathway on adventitial fibroblast (AF) migration in vitro.

Methods and Results—

Exogenous FGF-1 stimulated expression of OPN mRNA and protein in RASMCs in vitro in a dose- and time-dependent manner. OPN mRNA induction by FGF-1 was completely inhibited by either actinomycin D or cycloheximide, selective inhibitors of RNA polymerase and protein synthesis, respectively. OPN mRNA induction by FGF-1 was attenuated by PD 166866, a highly selective and potent FGFR-1 tyrosine kinase inhibitor. Addition of either PP2 or PD98059, specific inhibitors of Src and mitogen-activated extracellular signal–regulated kinase (MEK)/mitogen-activated protein (MAP) kinases, respectively, attenuated FGF-1–stimulated OPN mRNA expression. FGF-1 treatment of RASMCs enhanced RASMC-conditioned medium-stimulated AF migration; this effect was inhibited by pretreatment of RASMCs with either PD166866 or PP2. Immunodepletion of OPN from RASMC-conditioned medium inhibited both basal and FGF-1–stimulated AF migration.

Conclusions—

This in vitro study provided a first indication that ligand-activated FGFR-1 plays a significant role in upregulation of OPN expression at the transcriptional level via signaling to Src/MEK/MAP kinases in RASMCs and that this pathway is functionally significant in mediating AF migration via stimulation of OPN expression.
Microalbuminuria Reduction With Valsartan in Patients With Type 2 Diabetes Mellitus
Authors: Viberti Giancarlo , Wheeldon Nigel M.
Published: October 2002

Background

—

Elevated urine albumin excretion (UAER) is a modifiable risk factor for renal and cardiovascular disease in type 2 diabetes. Blockade of the renin-angiotensin system lowers UAER, but whether this effect is independent of blood pressure (BP) reduction remains controversial. The MicroAlbuminuria Reduction With VALsartan (MARVAL) study was designed to evaluate the BP-independent effect of valsartan on UAER in type 2 diabetic patients with microalbuminuria.

Methods and Results

—

Three hundred thirty-two patients with type 2 diabetes and microalbuminuria, with or without hypertension, were randomly assigned to 80 mg/d valsartan or 5 mg/d amlodipine for 24 weeks. A target BP of 135/85 mm Hg was aimed for by dose-doubling followed by addition of bendrofluazide and doxazosin whenever needed. The primary end point was the percent change in UAER from baseline to 24 weeks. The UAER at 24 weeks was 56% (95% CI, 49.6 to 63.0) of baseline with valsartan and 92% (95% CI, 81.7 to 103.7) of baseline with amlodipine, a highly significant between-group effect (
P
<0.001). Valsartan lowered UAER similarly in both the hypertensive and normotensive subgroups. More patients reversed to normoalbuminuria with valsartan (29.9% versus 14.5%;
P
=0.001). Over the study period, BP reductions were similar between the two treatments (systolic/diastolic 11.2/6.6 mm Hg for valsartan, 11.6/6.5 mm Hg for amlodipine) and at no time point was there a between-group significant difference in BP values in either the hypertensive or the normotensive subgroup.

Conclusions

—

For the same level of attained BP and the same degree of BP reduction, valsartan lowered UAER more effectively than amlodipine in patients with type 2 diabetes and microalbuminuria, including the subgroup with baseline normotension. This indicates a BP-independent antiproteinuric effect of valsartan.
Results and Long-Term Predictors of Adverse Clinical Events After Elective Percutaneous Interventions on Unprotected Left Main Coronary Artery
Authors: Takagi Takuro , Stankovic Goran , Finci Leo , Toutouzas Konstantinos , Chieffo Alaide , Spanos Vassilis , Liistro Francesco , Briguori Carlo , Corvaja Nicola , Albero Remo , Sivieri Ginevra , Paloschi Rossella , Di Mario Carlo , Colombo Antonio
Published: October 2002

Background

—

The safety and efficacy of percutaneous coronary intervention of de novo lesions in unprotected left main coronary arteries remains an unresolved issue.

Methods and Results

—

We analyzed 67 consecutive patients treated with the following devices: 39 with stents, 12 with rotational atherectomy plus stents, 13 with directional coronary atherectomy plus stents (a total of 64 patients were treated with stents), and 3 patients with directional coronary atherectomy only. The reference vessel size was 3.78±0.73 mm and lesion length was 6.6±3.0 mm. In-hospital complications were 2 coronary artery bypass grafts (CABGs) (3.0%), 2 Q-wave myocardial infarctions (MIs) (3.0%), and 3 non-Q-wave MIs (4.5%); there were no deaths. The estimated cardiac survival at 3 years was 91%. The cardiac mortality rate was higher in patients with Parsonnet score >15 versus ≤15 (21.4% versus 4.2%,
P
=0.02) at 3 years. The independent covariate of cardiac death was preserved left ventricular ejection fraction; for combined cardiac events (cardiac death, MI, repeat revascularization) it was large reference vessel size. Follow-up angiography at 5±2 months in 85% of eligible patients revealed 31.4% restenosis. Extending the follow-up to 31±23 months (19 patients with follow-up beyond 3 years) the cumulative event rates were 11 deaths (16.4%), 8 of them cardiac (11.9%), 2 (3.0%) MI, and 16 (23.9%) repeat revascularizations (CABG in 5 patients).

Conclusions

—

Elective percutaneous coronary intervention of de novo lesions in left main coronary arteries is feasible, with low procedural risk. The long-term follow-up revealed a high rate of angiographic restenosis and repeat revascularization, with a relatively high incidence of cardiac death. Reference vessel size and left ventricular function are the most important predictors of favorable follow-up.
Socioeconomic Disadvantage and Change in Blood Pressure Associated With Aging
Authors: Diez Roux Ana V. , Chambless Lloyd , Merkin Sharon Stein , Arnett Donna , Eigenbrodt Marsha , Nieto F. Javier , Szklo Moyses , Sorlie Paul
Published: October 2002

Background

—

Few studies have examined how the longitudinal change in blood pressure associated with aging differs across social groups within industrialized countries.

Methods and Results

—

Data from the Atherosclerosis Risk In Communities Study were used to investigate differences in the incidence of hypertension and in aging-related changes in blood pressure by neighborhood and individual socioeconomic factors over a 9-year follow-up. Disadvantage in multiple socioeconomic dimensions was associated with the greatest risk of developing hypertension (age- and sex-adjusted hazard ratio [HR] and 95% CI: HR 1.95, 95% CI 1.38 to 2.75 in whites and HR 1.43, 95% CI 0.96 to 2.13 in blacks). Aging-related increases in systolic blood pressure were inversely associated with socioeconomic position in whites (mean [SEM] 5-year increase in systolic blood pressure 7 [0.7] mm Hg in the most disadvantaged category and 5.4 [0.4] mm Hg in the most advantaged category). In whites, low socioeconomic position was also associated with more rapid declines in diastolic blood pressure after 50 years of age. Socioeconomic differences in hypertension incidence and changes in systolic blood pressure were reduced after adjustment for baseline blood pressure.

Conclusion

—

The change in blood pressure associated with aging varies by social groups within the United States.
Time Course of Sympathetic Neural Hyperactivity After Uncomplicated Acute Myocardial Infarction
Authors: Graham Lee N. , Smith Paul A. , Stoker John B. , Mackintosh Alan F. , Mary David A.S.G.
Published: October 2002

Background—

Little information is available on sympathetic activity after acute myocardial infarction (AMI), despite the belief that sympathetic drive is important in relation to morbidity and mortality. Indirect indices such as plasma catecholamines are transiently elevated after uncomplicated AMI, whereas other prognostically important autonomic indices may be affected longer. We planned to quantify central sympathetic output to the periphery after uncomplicated AMI and to investigate its progress over time.

Methods and Results—

After uncomplicated AMI, 13 patients had muscle sympathetic nerve activity (MSNA) assessed from multiunit discharges and from single units with defined vasoconstrictor properties (s-MSNA). Measurements were obtained 2 to 4 days after AMI and were repeated after 3 and 6 months. We also examined 3 matched control groups comprising normal subjects, patients with coronary artery disease, and hospitalized patients without AMI. MSNA and s-MSNA after AMI (84±4.6 bursts/100 beats and 95±5.8 impulses/100 beats) were unchanged at 3 months but decreased (
P
<0.01 and
P
<0.001) after 6 months (75±4.0 bursts/100 beats and 80±4.4 impulses/100 beats). These were still greater (at least
P
<0.01) than values in normal subjects, patients with coronary artery disease, and hospitalized patients without AMI (51±3.9 bursts/100 beats, 58±4.7 impulses/100 beats
;
56±2.2 bursts/100 beats, 61±2.2 impulses/100 beats; and 55±3.6 bursts/100 beats, 61±3.3 impulses/100 beats, respectively). This sympathetic hyperactivity was inversely correlated to left ventricular ejection fraction but not to changes in blood pressure.

Conclusions—

A protracted state of sympathetic hyperactivity was shown to occur after uncomplicated AMI. It is suggested that this hyperactivity may explain delayed cardiovascular morbidity and mortality and that it arises because of an impairment of reflexes from cardiac receptors.
Impaired Nitric Oxide Synthase Pathway in Diabetes Mellitus
Authors: Lin Ken Y. , Ito Akira , Asagami Tomoko , Tsao Philip S. , Adimoolam Shanthi , Kimoto Masumi , Tsuji Hideaki , Reaven Gerald M. , Cooke John P.
Published: October 2002

Background—

An endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), is elevated in patients with type 2 diabetes mellitus (DM). This study explored the mechanisms by which ADMA becomes elevated in DM.

Methods and Results—

Male Sprague-Dawley rats were fed normal chow or high-fat diet (n=5 in each) with moderate streptozotocin injection to induce type 2 DM. Plasma ADMA was elevated in diabetic rats (1.33±0.31 versus 0.48±0.08 μmol/L;
P
<0.05). The activity, but not the expression, of dimethylarginine dimethylaminohydrolase (DDAH) was reduced in diabetic rats and negatively correlated with their plasma ADMA levels (
P
<0.05). DDAH activity was significantly reduced in vascular smooth muscle cells and human endothelial cells (HMEC-1) exposed to high glucose (25.5 mmol/L). The impairment of DDAH activity in vascular cells was associated with an accumulation of ADMA and a reduction in generation of cGMP. In human endothelial cells, coincubation with the antioxidant polyethylene glycol–conjugated superoxide dismutase (22 U/mL) reversed the effects of the high-glucose condition on DDAH activity, ADMA accumulation, and cGMP synthesis.

Conclusions—

A glucose-induced impairment of DDAH causes ADMA accumulation and may contribute to endothelial vasodilator dysfunction in DM.
Hyperplastic Conotruncal Endocardial Cushions and Transposition of Great Arteries in Perlecan-Null Mice
Authors: Costell Mercedes , Carmona Rita , Gustafsson Erika , González-Iriarte Mauricio , Fässler Reinhard , Muñoz-Chápuli Ramón
Published: October 2002

Perlecan is a heparan-sulfate proteoglycan abundantly expressed in pericellular matrices and basement membranes during development. Inactivation of the perlecan gene in mice is lethal at two developmental stages: around E10 and around birth. We report a high incidence of malformations of the cardiac outflow tract in perlecan-deficient embryos. Complete transposition of great arteries was diagnosed in 11 out of 15 late embryos studied (73%). Three of these 11 embryos also showed malformations of semilunar valves. Mesenchymal cells in the outflow tract were abnormally abundant in mutant embryos by E9.5, when the endocardial-mesenchymal transformation starts in wild-type embryos. At E10.5, mutant embryos lacked well-defined spiral endocardial ridges, and the excess of mesenchymal cells obstructed sometimes the outflow tract lumen. Most of this anomalous mesenchyme expressed the smooth muscle cell-specific α-actin isoform, a marker of the neural crest in the outflow tract of the mouse. In wild-type embryos, perlecan is present in the basal surface of myocardium and endocardium, as well as surrounding presumptive neural crest cells. We suggest that the excess of mesenchyme at the earlier stages of conotruncal development precludes the formation of the spiral ridges and the rotation of the septation complex in order to achieve a concordant ventriculoarterial connection. The observed mesenchymal overpopulation might be due to an uncontrolled migration of neural crest cells, which would arrive prematurely to the heart. Thus, perlecan is involved in the control of the outflow tract mesenchymal population size, underscoring the importance of the extracellular matrix in cardiac morphogenesis.
Intrauterine Growth Retardation Is Associated With Reduced Activity and Expression of the Cationic Amino Acid Transport Systems y
+
/hCAT-1 and y
+
/hCAT-2B and Lower Activity of Nitric Oxide Synthase in Human Umbilical Vein Endothelial Cells
Authors: Casanello Paola , Sobrevia Luis
Published: October 2002

Intrauterine growth retardation (IUGR) is associated with vascular complications leading to hypoxia and abnormal fetal development. The effect of IUGR on
l
-arginine transport and nitric oxide (NO) synthesis was investigated in cultures of human umbilical vein endothelial cells (HUVECs). IUGR was associated with membrane depolarization and reduced
l
-arginine transport (
V
max
= 5.8±0.2 versus 3.3±0.1 pmol/μg protein per minute), with no significant changes in transport affinity (
K
m
=159±15 versus 137±14 μmol/L).
l
-Arginine transport was
trans
-stimulated (8- to 9-fold) in cells from normal and IUGR pregnancies. IUGR was associated with reduced production of
l
-[
3
H]citrulline from
l
-[
3
H] arginine, lower nitrite and intracellular
l
-arginine,
l
-citrulline, and cGMP. IUGR decreased hCAT-1 and hCAT-2B mRNA, and increased eNOS mRNA and protein levels. IUGR-associated inhibition of
l
-arginine transport and NO synthesis, and membrane depolarization were reversed by the NO donor
S
-nitroso-
N
-acetyl-
l
,
d
-penicillamine. In summary, endothelium from fetuses with IUGR exhibit altered
l
-arginine transport and NO synthesis (
l
-arginine/NO pathway), reduced expression and activity of hCAT-1 and hCAT-2B and reduced eNOS activity. Alterations in
l
-arginine/NO pathway could be critical for the physiological processes involved in the etiology of IUGR in human pregnancies.
Aldose Reductase Is an Obligatory Mediator of the Late Phase of Ischemic Preconditioning
Authors: Shinmura Ken , Bolli Roberto , Liu Si-Qi , Tang Xian-Liang , Kodani Eitaro , Xuan Yu-ting , Srivastava Sanjay , Bhatnagar Aruni
Published: October 2002

Aldose reductase (AR), a member of the aldo-keto reductase superfamily, has been shown to metabolize toxic aldehydes generated by lipid peroxidation, suggesting that it may serve as an antioxidant defense. To investigate its role in the late phase of ischemic preconditioning (PC), conscious rabbits underwent 6 cycles of 4-minute coronary occlusion/4-minute reperfusion. Twenty-four hours later, there was a marked increase in AR protein and activity and in the myocardial content of sorbitol, a unique product of AR catalysis. Pretreatment with
N
ω
-nitro-
l
-arginine, a nitric oxide synthase inhibitor, or chelerythrine, a protein kinase C inhibitor (both given at doses that block late PC in this model), prevented the increase in AR protein 24 hours later, demonstrating that ischemic PC upregulates AR via nitric oxide- and protein kinase C-dependent signaling pathways. The AR-selective inhibitors tolrestat and sorbinil prevented AR-mediated accumulation of sorbitol and abrogated the infarct-sparing effect of late PC, demonstrating that enhanced AR activity is necessary for this cardioprotective phenomenon to occur. Inhibition of AR did not affect infarct size or the myocardial accumulation of the lipid peroxidation product 4-hydroxy
trans
-2-nonenal (HNE) in nonpreconditioned rabbits. The accumulation of HNE was inhibited by late PC, and this effect was abrogated by sorbinil. Taken together, these results establish AR as an essential mediator of late PC. Furthermore, the data suggest that myocardial ischemia/reperfusion injury is due in part to the generation of lipid peroxidation products and that late PC diminishes this source of injury by upregulating AR.
Functional Compartmentation of Endothelial P2Y Receptor Signaling
Authors: Kaiser Robert A. , Oxhorn Brian C. , Andrews Gracie , Buxton Iain L.O.
Published: October 2002

The presence of multiple receptors for disparate nucleotides on endothelial cells makes it unclear how the endothelium differentiates among these signals. We propose that endothelial P2Y receptors are organized into cholesterol-rich signaling domains, such as caveolae and respond to nucleotide agonists by mobilizing intracellular calcium. Treatment of endothelial cells with 5 mmol/L β-methyl-cyclodextrin prevents calcium release in response to the nucleotide receptor agonists 2-methylthio-ATP, ATP, ADP, and UTP, but not the kinin receptor agonist bradykinin, suggesting that depletion of membrane cholesterol disrupts signaling at P2Y receptors and that bradykinin receptors are not prelocalized to cholesterol microdomains in these cells. Direct measurement of cholesterol content after β-methyl-cyclodextrin treatment of aortic rings reveals a concentration-dependent depletion of cholesterol that parallels functional antagonism of P2Y-mediated relaxation. Nucleotide- and bradykinin-mediated relaxation is disrupted by 5 to 15 mmol/L β -methyl-cyclodextrin treatment or 1 to 10 μg/mL filipin III in a concentration-dependent fashion. Norepinephrine contracted aorta treated with A23187 relaxes in an endothelium-dependent fashion despite depletion of 84% of membrane-extractable cholesterol. These data indicate that in the basal state, P2Y receptors but not the kinin receptor may be compartmented to cholesterol-dependent signaling domains in guinea pig endothelium and that cholesterol-rich microdomains in these cells can respond to intracellular calcium in an agonist-specific manner. We suggest that the functional organization of cholesterol-rich signaling microdomains allows agonist-specific responses to increases in intracellular calcium and that this property may be a general phenomenon that permits cells to respond disparately to agonists that may signal through common calcium release pathways.
Protease-Activated Receptor-2 Stimulates Angiogenesis and Accelerates Hemodynamic Recovery in a Mouse Model of Hindlimb Ischemia
Authors: Milia Anna F. , Salis Maria B. , Stacca Tiziana , Pinna Alessandra , Madeddu Paolo , Trevisani Marcello , Geppetti Pierangelo , Emanueli Costanza
Published: October 2002

Proteinase-activated receptors (PAR-2) are expressed by the cardiovascular system and mediate vasodilation, plasma protein extravasation, and endothelial cell proliferation, all regarded as essential steps for neovascularization. We investigated the angiogenic action of PAR-2 signaling in vivo. The effect of the PAR-2 activating peptide (PAR-2AP, SLIGRL-NH
2
) was assessed in the absence of ischemia, and the therapeutic potential of PAR-2AP and the PAR-2 agonist trypsin (at 300 and 1.5 nmol IM daily for 21 days, respectively) was also tested in mice subjected to unilateral limb ischemia. PAR-2AP increased capillarity in normoperfused adductor skeletal muscles, whereas neither the vehicle of the PAR2-AP nor the PAR-2 reverse peptide (PAR-2RP, LRGILS-NH
2
) did produce any effect. In addition, both PAR-2AP and trypsin enhanced reparative angiogenic response to limb ischemia, an effect that was not produced by PAR-2RP or the vehicle of PAR-2 agonists. Potentiation of reparative angiogenesis by PAR-2AP or trypsin resulted in an accelerated hemodynamic recovery and enhanced limb salvage. In conclusions, our study is the first to demonstrate the angiogenic potential of PAR-2 stimulation in vivo. If similar effects occur in humans, PAR-2AP agonists could have some therapeutic potential for the treatment of tissue ischemia.
Assessment of Functioning and Disability After Ischemic Stroke
Authors: Weimar Christian , Kurth Tobias , Kraywinkel Klaus , Wagner Markus , Busse Otto , Haberl Roman Ludwig , Diener Hans-Christoph
Published: October 2002

Background and Purpose

—

Functioning and disability after ischemic stroke are clinically meaningful and of major relevance to patients. Despite many instruments available to assess these outcomes, little is known about their interrelation and predictive factors.

Methods

—

We prospectively identified 4264 patients with acute ischemic stroke from 30 hospitals in Germany during a 1-year period between 1998 and 1999 and registered them in a common data bank. The patients were centrally followed up via telephone interview after 100 days and 1 year to assess various scales such as the Barthel Index (BI), modified Rankin Scale (MRS), extended Barthel Index (EBI), Short Form-36 Physical Functioning (SF-36 PF), and Center for Epidemiologic Studies–Depression short form (CES-D).

Results

—

Outcome status could be assessed in 67.2% of patients 100 days after hospital admission. Of these, 13.9% had died, 53.7% had regained functional independence (BI <95), 46.3% had no or mild residual symptoms (MRS ≤1), and 44.6% had no higher cognitive deficits on the EBI. Of the patients who personally answered the follow-up questions, 67% had no major physical disability (SF-36 PF <60), and 32.9% reported symptoms classified as depression (CES-D ≥10). The high percentage of patients reaching the maximum score (ceiling effect) in the BI was less pronounced in the MRS and SF-36 PF. The predictive factors for dichotomized outcomes on each scale were similar for adverse functioning and disability but varied considerably for depression.

Conclusions

—

To avoid ceiling effects in outcome distribution of patients treated in specialized stroke centers, the MRS and SF-36 PF instruments are preferable to the BI. Parametric use of the SF-36 PF could further improve outcome measurement by considering individual treatment effects.
Predictors of Hemorrhagic Transformation After Intravenous Recombinant Tissue Plasminogen Activator
Authors: Selim Magdy , Fink John N. , Kumar Sandeep , Caplan Louis R. , Horkan Clare , Chen Yi , Linfante Italo , Schlaug Gottfried
Published: October 2002

Background and Purpose
—

Hemorrhagic transformation (HT) is a potentially dangerous complication of thrombolytic therapy. Recent studies suggest that diffusion-weighted MRI (DWI) can help to predict the risk of intracerebral hemorrhage (ICH) after thrombolysis. We sought to examine which pretreatment DWI parameters and clinical data are predictive of ICH after intravenous thrombolysis.

Methods

—

We retrospectively reviewed our prospective stroke database for patients with ischemic stroke treated with intravenous recombinant tissue plasminogen activator (rtPA) within 3 hours from symptom onset who had DWI before treatment and MRI with T2* sequence or CT 24 to 48 hours later to assess for ICH over the past 4 years. We measured the volumes and voxel-by-voxel apparent diffusion coefficient (ADC) values of the initial DWI lesions and retrieved demographic data, risk factors, National Institutes of Health Stroke Scale (NIHSS) scores on admission, and blood tests results. We examined several variables using univariate and multivariate regression analyses to determine predictors of ICH.

Results

—

Twenty-nine patients fulfilled our inclusion criteria; 17 patients (58%) had ICH, and of these 4 (13%) had symptomatic ICH and fatal outcome. On univariate analysis, higher systolic blood pressure, NIHSS score, serum glucose level, volume of initial DWI lesion, and absolute number of voxels with ADC value ≤550×10
−6
mm
2
/s were statistically associated with ICH, and all were subjected to multivariate analysis. However, only the absolute number of voxels, ie, volume of ischemic tissue on DWI, with ADC ≤550×10
−6
mm
2
/s emerged as an independent predictor of ICH.

Conclusions

—

Our findings suggest that volumetric ADC analysis can be used to assess ICH risk after thrombolysis. This may be particularly helpful if rtPA is to be given outside the 3-hour window.
Why Democracies Cooperate More: Electoral Control and International Trade Agreements
Authors: Mansfield Edward D. , Milner Helen V. , Rosendorff B. Peter
Published: October 2002

Over the past fifty years, barriers to international trade have decreased substantially. A key source of this decline in protectionism has been the proliferation of agreements among countries to liberalize commerce. In this article, we analyze the domestic political conditions under which states have concluded such agreements and, more generally, explore the factors affecting interstate economic cooperation. We argue that interstate cooperation on commercial issues depends heavily on the political regime types of participants: as states become more democratic, they are increasingly likely to conclude trade agreements. To test our claim, we examine whether the regime types of states have influenced their propensity to form and expand preferential trading arrangements (PTAs) during the period since World War II. We find that democratic countries are about twice as likely to form a PTA as autocratic countries, and that pairs of democracies are roughly four times as likely to do so as autocratic pairs. These results provide strong evidence that democracies are more commercially cooperative than less democratic countries.
New Naturality: A Generative Approach to Art and Design
Authors: Soddu Celestino
Published: October 2002

In the field of generative art and design, design concepts are represented as code. This generative code functions as DNA does in nature. It uses artificial life to generate a multiplicity of possible artworks, artificial events, architectures and virtual environments. In the generative approach the real artwork is not merely a product, such as an image or 3D model. The generative artwork is an Idea-Product. It represents an artificial species able to generate an endless sequence of individual events, each one different, unique and unrepeatable but belonging to the same identifiable design Idea. The author's project, Argenia, realizes the “new naturality” of artificial objects.
Class-Based Probability Estimation Using a Semantic Hierarchy
Authors: Clark Stephen , Weir David
Published: October 2002

This article concerns the estimation of a particular kind of probability, namely, the probability of a noun sense appearing as a particular argument of a predicate. In order to overcome the accompanying sparse-data problem, the proposal here is to define the probabilities in terms of senses from a semantic hierarchy and exploit the fact that the senses can be grouped into classes consisting of semantically similar senses. There is a particular focus on the problem of how to determine a suitable class for a given sense, or, alternatively, how to determine a suitable level of generalization in the hierarchy. A procedure is developed that uses a chi-square test to determine a suitable level of generalization. In order to test the performance of the estimation method, a pseudo-disambiguation task is used, together with two alternative estimation methods. Each method uses a different generalization procedure; the first alternative uses the minimum description length principle, and the second uses Resnik's measure of selectional preference. In addition, the performance of our method is investigated using both the standard Pearson chi-square statistic and the log-likelihood chi-square statistic.
Independent Components of Magnetoencephalography: Localization
Authors: Tang Akaysha C. , Pearlmutter Barak A. , Malaszenko Natalie A. , Phung Dan B. , Reeb Bethany C.
Published: October 2002

We applied second-order blind identification (SOBI), an independent component analysis method, to MEG data collected during cognitive tasks. We explored SOBI's ability to help isolate underlying neuronal sources with relatively poor signal-to-noise ratios, allowing their identification and localization. We compare localization of the SOBI-separated components to localization from unprocessed sensor signals, using an equivalent current dipole modeling method. For visual and somatosensory modalities, SOBI preprocessing resulted in components that can be localized to physiologically and anatomically meaningful locations. Furthermore, this preprocessing allowed the detection of neuronal source activations that were otherwise undetectable. This increased probability of neuronal source detection and localization can be particularly beneficial for MEG studies of higher-level cognitive functions, which often
A Survey of Usability Evaluation in Virtual Environments: Classification and Comparison of Methods
Authors: Bowman Doug A. , Gabbard Joseph L. , Hix Deborah
Published: October 2002

Virtual environments (VEs) are a relatively new type of human–computer interface in which users perceive and act in a three-dimensional world. The designers of such systems cannot rely solely on design guidelines for traditional two-dimensional interfaces, so usability evaluation is crucial for VEs. This paper presents an overview of VE usability evaluation to organize and critically analyze diverse work from this field. First, we discuss some of the issues that differentiate VE usability evaluation from evaluation of traditional user interfaces such as GUIs. We also present a review of some VE evaluation methods currently in use, and discuss a simple classification space for VE usability evaluation methods. This classification space provides a structured means for comparing evaluation methods according to three key characteristics: involvement of representative users, context of evaluation, and types of results produced. Finally, to illustrate these concepts, we compare two existing evaluation approaches: testbed evaluation (Bowman, Johnson, & Hodges, 1999) and sequential evaluation (Gabbard, Hix, & Swan, 1999).
Self-Reproduction in Three-Dimensional Reversible Cellular Space
Authors: Imai Katsunobu , Hori Takahiro , Morita Kenichi
Published: October 2002

Due to inevitable power dissipation, it is said that nano-scaled computing devices should perform their computing processes in a reversible manner. This will be a large problem in constructing three-dimensional nano-scaled functional objects. Reversible cellular automata (RCA) are used for modeling physical phenomena such as power dissipation, by studying the dissipation of garbage signals. We construct a three-dimensional self-inspective self-reproducing reversible cellular automaton by extending the two-dimensional version SR8. It can self-reproduce various patterns in three-dimensional reversible cellular space without dissipating garbage signals.
Hollywood Glamour and Mass Consumption in Postwar Italy
Authors: Gundle Stephen
Published: October 2002

Italian society after World War II was profoundly affected by the culture of “glamour” that encouraged mass consumption. This culture drew heavily on images and desires created by the American film industry, and it would not have arisen in the absence of American glamour. Over time, however, Italian glamour acquired some important indigenous features, which were economically beneficial for Italy in boosting exports and tourism. Through most of the Cold War, the perceived glamour of Rome captured in the film La Dolce Vita made the city a cosmopolitan crossroads for the rich and famous. Nevertheless, in contrast to the United States, which was the avatar of glamour, Italy did not develop domestic glamour in the full sense of the term.
Compendium of the genus Criconemoides Taylor, 1936 (Nematoda: Criconematidae)
Authors: Loof Pieter , Brzeski Michał , Choi Young Euon
Published: October 2002

The genus Criconemoides is diagnosed and lists are given of the valid species with their synonyms, of species inquirendae vel dubiae and of departures. The main diagnostic features of the species included are presented in tabular form.
Compendium of the genus Mesocriconema Andrássy, 1965 (Nematoda: Criconematidae)
Authors: Choi Young Euon , Loof Pieter , Brzeski Michał
Published: October 2002

The genus Mesocriconema is diagnosed and 90 valid species and their synonyms are listed. The main diagnostic characteristics of the species included are presented in tabular form. The synonymy of Pakcriconemoides with Mesocriconema is supported.
Panagrobelus stammeri Rühm, 1956 and Plectonchus hunti n. sp.: implications of new morphological observations for characterisation of these genera (Nematoda: Panagrolaimoidea)
Authors: Baldwin James , De Ley Paul , Mundo-Ocampo Manuel , Nadler Steven , Stock S. Patricia , De Ley Irma
Published: October 2002

A detailed morphological description (light and scanning electron microscope observations) is given of two isolates currently used in molecular and developmental studies: PDL0024, Panagrobelus stammeri Rühm, 1956 and PDL0025, a new species herein described as Plectonchus hunti n. sp. We redescribe the lip region, interpret the orientation of the lips in P.stammeri and provide additional morphological and morphometric diagnostic features. Plectonchus hunti n. sp. is characterised by the bifurcating spicule tip and by the placement of the male genital papillae in a 3/3 + p + 2 arrangement. Additionally, females of this new species can be differentiated from other species of Plectonchus by the more anterior position of the vulva, the more anterior location of the excretory pore and the tail morphology. An emended diagnosis for this genus is provided. In this study we demonstrate that both studied taxa share morphological similarities, such as the presence of a 'cephaloboid-type' spermatheca. Our observations also indicate slight but consistent differences in cell composition of the female reproductive system between these two taxa.
Rta of the human herpesvirus 8/Kaposi sarcoma–associated herpesvirus up-regulates human interleukin-6 gene expression
Authors: Deng Hongyu , Chu Julia T. , Rettig Matthew B. , Martinez-Maza Otoniel , Sun Ren
Published: October 2002

Human herpesvirus 8 (HHV-8)/Kaposi sarcoma–associated herpesvirus (KSHV) is linked to a number of malignancies thought to be driven by cytokines, including interleukin-6 (IL-6). Rta, a transcriptional activator encoded by HHV-8/KSHV, activates the viral lytic cycle leading to the expression of several viral genes implicated in viral pathogenesis. However, the effect of HHV-8/KSHV Rta on cellular genes has not been reported. We present evidence that the human IL-6(hIL-6) gene is up-regulated by Rta. Rta potently activated (up to 164-fold) the hIL-6 promoter in a dose-dependent manner in a transient transfection reporter system. Rta also induced expression of the endogenous hIL-6 gene, as shown by enzyme-linked immunosorbent assays. Activation of the hIL-6gene by HHV-8/KSHV supports the role of hIL-6 in the development of these malignancies.
Expression and subcellular localization of NRAMP1 in human neutrophil granules
Authors: Canonne-Hergaux François , Calafat Jero , Richer Etienne , Cellier Mathieu , Grinstein Sergio , Borregaard Neils , Gros Philippe
Published: October 2002

Mutations at the Nramp1 gene cause susceptibility to infections with intracellular pathogens. In human blood, polymorphonuclear (PMN) leukocytes are the most abundant site ofNRAMP1 messenger RNA (mRNA) expression, suggesting that NRAMP1 plays an important role in the activity of these cells. By Northern blot analysis, NRAMP1 mRNA was only detected in most mature neutrophils from bone marrow (band and segmented cells). A high-affinity polyclonal rabbit antihuman NRAMP1 antibody directed against the amino terminus of the protein was produced and used to study cellular and subcellular localization of the protein in primary human neutrophils. Subcellular fractionation of granule populations together with immunoblotting studies with granule-specific markers indicate that NRAMP1 expression is primarily in tertiary granules. These granules are positive for the matrix enzyme gelatinase and the membrane subunit of the vacuolar H+/ATPase and can be recruited for exocytosis by treatment of neutrophils with phorbol myristate acetate. Immunogold studies by cryoelectron microscopy with primary neutrophils confirm that a majority (75%) of NRAMP1-positive granules are also positive for gelatinase, but they also suggest further heterogeneity in this granule population. Presence of NRAMP1 in tertiary granules is in agreement with the late-stage appearance ofNRAMP1 mRNA during neutrophil maturation in bone marrow. Finally, immunofluorescence studies of Candida albicans–containing phagosomes formed in neutrophils indicate that NRAMP1 is recruited from tertiary granules to the phagosomal membrane on phagocytosis, supporting a role for NRAMP1 in the antimicrobial defenses of human neutrophils.
Transferrin receptor hyperexpression in primary erythroblasts is lost on transformation by avian erythroblastosis virus
Authors: Lobmayr Lioba , Sauer Thomas , Killisch Iris , Schranzhofer Matthias , Wilson Robert B. , Ponka Prem , Beug Hartmut , Müllner Ernst W.
Published: October 2002

In primary chicken erythroblasts (stem cell factor [SCF] erythroblasts), transferrin receptor (TfR) messenger RNA (mRNA) and protein were hyperexpressed as compared to nonerythroid chicken cell types. This erythroid-specific hyperexpression was abolished in transformed erythroblasts (HD3E22 cells) expressing the v-ErbA and v-ErbB oncogenes of avian erythroblastosis virus. TfR expression in HD3E22 cells could be modulated by changes in exogenous iron supply, whereas expression in SCF erythroblasts was not subject to iron regulation. Measurements of TfR mRNA half-life indicated that hyperexpression in SCF erythroblasts was due to a massive stabilization of transcripts even in the presence of high iron levels. Changes in mRNA binding activity of iron regulatory protein 1 (IRP1), the primary regulator of TfR mRNA stability in these cells, correlated well with TfR mRNA expression; IRP1 activity in HD3E22 cells and other nonerythroid cell types tested was iron dependent, whereas IRP1 activity in primary SCF erythroblasts could not be modulated by iron administration. Analysis of avian erythroblasts expressing v-ErbA alone indicated that v-ErbA was responsible for these transformation-specific alterations in the regulation of iron metabolism. In SCF erythroblasts high amounts of TfR were detected on the plasma membrane, but a large fraction was also located in early and late endosomal compartments, potentially concealing temporary iron stores from the IRP regulatory system. In contrast, TfR was almost exclusively located to the plasma membrane in HD3E22 cells. In summary, stabilization of TfR mRNA and redistribution of Fe-Tf/TfR complexes to late endosomal compartments may contribute to TfR hyperexpression in primary erythroblasts, effects that are lost on leukemic transformation.
A human Mix-like homeobox gene MIXL shows functional similarity to Xenopus Mix.1
Authors: Guo Wei , Pui-yee Chan Agnes , Liang Hong , Wieder Eric D. , Molldrem Jeffrey J. , Etkin Laurence D. , Nagarajan Lalitha
Published: October 2002

Molecular events involved in specification of early hematopoietic system are not well known. In Xenopus, a paired-box homeodomain family (Mix.1-4) has been implicated in this process. Although Mix-like homeobox genes have been isolated from chicken (CMIX) and mice (Mml/MIXL1), isolation of a human Mix-like gene has remained elusive. We have recently isolated and characterized a novel human Mix-like homeobox gene with a predicted open reading frame of 232 amino acids designated the Mix.1 homeobox (Xenopus laevis)–like gene (MIXL). The overall identity of this novel protein to CMIX and Mml/MIXL1 is 41% and 69%, respectively. However, the identity in the homeodomain is 66% to that of Xenopus Mix.1, 79% to that of CMIX, and 94% to that of Mml/MIXL1. In normal hematopoiesis, MIXL expression appears to be restricted to immature B- and T-lymphoid cells. Several acute leukemic cell lines of B, T, and myeloid lineage express MIXL suggesting a survival/block in differentiation advantage. Furthermore, Xenopus animal cap assay revealed that MIXL could induce expression of the α-globin gene, suggesting a functional conservation of the homeodomain. Isolation of theMIXL gene is the first step toward understanding novel regulatory circuits in early hematopoietic differentiation and malignant transformation.
Expression of the β4 integrin subunit induces monocytic differentiation of 32D/v-Abl cells
Authors: Morena Annarita , Riccioni Sabrina , Marchetti Alessandra , Polcini Alessandro Tartaglia , Mercurio Arthur M. , Blandino Giovanni , Sacchi Ada , Falcioni Rita
Published: October 2002

The α6β4 integrin is the receptor for various laminin isoforms and is a component of the hemidesmosome. Increased expression levels of this integrin correlate with the aggressive phenotype of many epithelial tumors compared with surrounding normal tissue. Furthermore, the long cytoplasmic tail of the β4 integrin subunit has been implicated in several signal transduction pathways that are involved not only in invasion, but also in proliferation and apoptosis. Here we report that the exogenous expression of β4 integrin in 32D/v-abl–transformed cells reduces tumor aggressiveness in vivo and strongly inhibits cell proliferation in vitro by inducing monocytic differentiation. These effects are accompanied by growth arrest and p73 protein accumulation. The hypothesis that the inhibition of v-Abl oncogenic capacity could allow the activation of the endogenous c-Abl was tested in RKO cells. The results clearly demonstrated a strong increase of c-Abl phosphorylation that is accompanied by its association with p73 protein. Overall, the reported findings indicate that α6β4 integrin promotes growth arrest and differentiation by modulating Abl kinases and p73 protein pathway(s).