bluuebunny/crossref_metadata_2025 huggingface dataset:
MODEL FOR THE GROWTH OF BACTERIAL GENOMES
Authors: HSIEH L. C. , LEE H. C.
Published: October 2002

Analysis of the frequency of occurrence of short oligonucleotides in typical bacterial genomes reveals that they exhibit the statistical characteristics of a DNA sequence of a much shorter length. This peculiar property suggests a model for genome growth in which a genome evolves by random mutation but primarily grows by random segmental self-copying. Computer-generated genome sequence based on this model indeed has statistical properties similar to those of bacterial genomes.
ELECTRONIC STATES IN A CYLINDRICAL QUANTUM DOT IN THE PRESENCE OF PARALLEL ELECTRICAL AND MAGNETIC FIELDS
Authors: SARKISYAN H. A.
Published: October 2002

In this article, we investigate an exactly solvable model, describing the behavior of electrons in a cylindrical quantum dot GaAs / Ga 1-x Al x As with parabolic confinement potential under the influence of external electrical and magnetic fields, directed along the axes of the cylinder. The wave-function and energy levels of the electron are found. An exact analytical expression for the energy of Stark shift is obtained. It has been shown that only the quadratic Stark effect takes place in the considered system. On the basis of the obtained results, the coefficient of direct interband transition in the system is calculated.
Antithrombotic Effect of Captopril and Losartan Is Mediated by Angiotensin-(1-7)
Authors: Kucharewicz Iwona , Pawlak Robert , Matys Tomasz , Pawlak Dariusz , Buczko Wlodzimierz
Published: October 2002

It is well established that renin-angiotensin system blockers exert NO/prostacyclin-dependent antithrombotic effects. Because some beneficial effects of these drugs are mediated by angiotensin (Ang)-(1-7), in the present study we examined if their antithrombotic action could be mediated by Ang-(1-7). Intravenous infusion of Ang-(1-7) (1, 10, or 100 pmol/kg per minute for 2 hours) into rats developing venous thrombosis caused 50% to 70% reduction of the thrombus weight. This effect was dose-dependently reversed by cotreatment with A-779 (selective Ang-[1-7] receptor antagonist) or EXP 3174 (angiotensin type 1 receptor antagonist) but not by PD 123,319 (angiotensin type 2 receptor antagonist). Similarly, the antithrombotic effects of captopril (ACE inhibitor) and losartan (angiotensin type 1 receptor blocker) were attenuated by A-779 in a dose-dependent manner. The effect of Ang-(1-7) was completely abolished by concomitant administration of NO synthase inhibitor (
N
G
-nitro-
l
-arginine methyl ester) and prostacyclin synthesis inhibitor (indomethacin), as has been shown previously for captopril and losartan. Thus, the antithrombotic effect of renin-angiotensin system blockers involves Ang-(1-7)–evoked release of NO and prostacyclin.
Hypertension, Insulin, and Proinsulin in Participants With Impaired Glucose Tolerance
Authors:   The Diabetes Prevention Program Research Group
Published: October 2002

The association of insulin resistance and hyperinsulinemia to blood pressure has remained controversial. We examined the association of insulinemia to hypertension and blood pressure using baseline measurements for participants of the Diabetes Prevention Program (DPP). The DPP is a multicenter randomized controlled trial of 3819 participants with impaired glucose tolerance, and is designed to evaluate interventions for the delay or prevention of type 2 diabetes. The relationship between hypertension and insulinemia is described overall and by ethnicity. The effects of demographics (age and gender), adiposity, and glucose on the relationship are also presented. Asian Americans and African Americans had a similarly high prevalence of hypertension as did whites; American Indians had a lower prevalence of hypertension. Among participants not on antihypertensive medications, systolic blood pressure was significantly (but weakly) correlated with fasting insulin (
r
=0.12), homeostasis model assessment of insulin resistance (HOMA IR;
r
=0.13), and fasting proinsulin (
r
=0.10) when adjusted for age and gender (all,
P
<0.001). Systolic blood pressure showed similar correlations to fasting insulin in each ethnic group. After further adjustment for body mass index, the association of fasting insulin to systolic and diastolic blood pressures weakened considerably but remained significant (systolic:
r
=0.06,
P
=0.002; DBP:
r
=0.06,
P
<0.001). We conclude that a weak but significant association between insulin, (and proinsulin and HOMA IR) and blood pressure exists but is largely explained by overall adiposity. This association is similar among ethnicities, with the possible exception of Hispanics. The relation between insulin concentrations and blood pressure explains relatively little of the ethnic differences in hypertensive prevalence.
Genome Scan Among Nigerians Linking Blood Pressure to Chromosomes 2, 3, and 19
Authors: Cooper Richard S. , Luke Amy , Zhu Xiaofeng , Kan Donghui , Adeyemo Adebowale , Rorimi Charles , Bouzekri Nourdine , Ward Ryk
Published: October 2002

An understanding of the genetic influences on hypertension would help unravel the pathophysiology of this complex disorder and improve our understanding of causal mechanisms. Contemporary technology makes it possible to examine enough genetic markers to support a generalized search across the entire genome for candidate regions. In the present study, a family set was recruited from southwest Nigeria, and 378 microsatellite markers were typed on 792 individuals in 196 families. Multipoint variance component analysis identified linkage signals (logarithm of the odds [LOD] 1.74,
P
<0.0023) for systolic blood pressure on 19p (D19S714) and 19q (D19S246), whereas for diastolic blood pressure, linkage was observed on 2p (D2S1790), 3p (D3S1304), 5q (D5S1462), 7p (D7S3046), 7q (D7S821), and 10q (D10S1221). Other regions of interest (1.18<LOD<1.74, 0.0023<
P
<0.01) were found on chromosomes 1, 6, 8, 9, and 11. These results provide additional evidence of linkage between blood pressure and several genomic regions reported in previous studies. Some of these regions additionally harbor hypertension candidate genes. Although evidence of linkage for blood pressure has been very slow to accumulate, even in comparison to other complex traits, the sum of current evidence appears to implicate, in particular, 2p, 3p, and 19p. Study designs that make it possible to confirm these results with association analysis and narrow the genomic interval are needed in order to make progress in this field.
Interaction of Sildenafil With cAMP-Mediated Vasodilation In Vivo
Authors: Schalcher Christoph , Schad Karin , Brunner-La Rocca Hans Peter , Schindler Ruth , Oechslin Erwin , Scharf Christoph , Suetsch Gabor , Bertel Osmund , Kiowski Wolfgang
Published: October 2002

Sildenafil inhibits cGMP breakdown by phosphodiesterase 5. In vitro, increased cGMP levels inhibit cAMP breakdown by phosphodiesterase 3. It is uncertain, however, whether sildenafil increases biological effects of interventions increasing cAMP levels in vivo. The objective of the present study in 40 healthy male volunteers was to determine the existence and extent of interactions with sildenafil and vasodilators acting via cGMP or cAMP or independently from these mediators on the arterial tone of the human forearm. Forearm blood flow (FBF) responses (plethysmography) to brachial artery infusions of 3 doses each of nitroglycerin, which increases cGMP levels; of isoprenaline and milrinone, which increase cAMP levels; and of verapamil as a control were assessed at baseline and 80 minutes after 50 mg oral sildenafil in 10 volunteers each. Sildenafil increased FBF (2.5±0.1 to 3.5±0.2 mL/min per 100 mL,
P
<0.001; n=40). At equipotent vasodilator dosages, sildenafil increased FBF from 7.5±1.0 to 9.8±1.2 mL/min per 100 mL for nitroglycerin, from 8.3±1.0 to 10.4±1.4 mL/min per 100 mL for isoprenaline, and from 8.1±1.0 to 10.3±1.2 mL/min per 100 mL for milrinone and slightly decreased FBF from 7.7±1.3 to 7.1±1.2 mL/min per 100 mL for verapamil. ANOVA for repeated measures revealed a significant interaction between sildenafil and the type of vasodilator on FBF (
P
<0.01). The responses of FBF to nitroglycerin, milrinone, and isoprenaline after sildenafil were similarly increased compared with the response to verapamil (
P
<0.01). Sildenafil markedly enhanced the arterial vasodilator response to nitroglycerin, milrinone, and isoprenaline. The response to milrinone and isoprenaline is compatible with an interaction between cGMP and phosphodiesterase 3 or an enhancement of the NO component of cAMP-mediated vasodilation, and raises the possibility of enhanced biological effects of interventions leading to increases of cAMP in the presence of sildenafil.
Kallikrein Gene Delivery Improves Cardiac Reserve and Attenuates Remodeling After Myocardial Infarction
Authors: Agata Jun , Chao Lee , Chao Julie
Published: October 2002

In this study, we used the somatic gene delivery approach to explore the role of the kallikrein-kinin system (KKS) in cardiac remodeling and apoptosis after myocardial infarction (MI). Rats were subjected to coronary artery ligation to induce MI, and adenovirus carrying the human tissue kallikrein or luciferase gene was injected into the tail vein at 1 week after surgery. Cardiac output gradually decreased from 2 to 6 weeks after MI, whereas delivery of the kallikrein gene prevented this decrease. Cardiac responses to dobutamine-induced stress were improved in rats receiving kallikrein gene as compared with rats receiving control virus at 6 weeks after MI. Kallikrein significantly improved cardiac remodeling by decreasing collagen density, cardiomyocyte size, and left ventricular internal perimeter and increasing capillary density in the heart at 6 weeks after MI. Kallikrein gene transfer attenuated myocardial apoptosis, which was positively correlated with remodeling parameters in the heart at 2 weeks after MI. Endothelial dysfunction, characterized by increased vascular resistance, decreased left ventricular blood flow, and decreased cardiac nitric oxide levels, existed in remodeled hearts at 2 weeks after MI, whereas kallikrein gene transfer improved these parameters. Kallikrein gene delivery improved cell survival parameters as shown by increased phospho-Akt and reduced caspase-3 activation at 2 weeks after MI. This study indicates that the kallikrein-kinin system plays an important role in preventing the progression of heart failure by attenuating cardiac hypertrophy and fibrosis, improving endothelial function, and inhibiting myocardial apoptosis through the Akt-mediated signaling pathway.
Circadian Differences in Stress-Induced Pressor Reactivity in Mice
Authors: Bernatova Iveta , Key Mary P. , Lucot James B. , Morris Mariana
Published: October 2002

The objective of this study was to determine the effect of chronic stress exposure on the circadian pattern of cardiovascular responses in mice. Using male C57BL6 mice with carotid arterial catheters, we tested the effect of 7 days of intermittent shaker stress on body weight, food intake, drinking activity, plasma corticosterone, mean arterial pressure (MAP), and heart rate. The stress was delivered automatically for 2-minute periods (150 cycles/min), 45 times/d for 7 days. Plasma corticosterone was significantly increased in acutely and chronically stressed mice, with a partial attenuation in the chronic condition. Stress increased water intake, produced no change in food intake, and significantly decreased body weight (5% change). MAP and heart rate were measured continuously on stress days 1, 3, and 7 and during the basal and recovery periods. Chronic stress did not produce a sustained increase in MAP; however, there was an increase in MAP during the first stress day and a decrease during the recovery period. There was a circadian pattern in the pressor responses, with greater increases seen during the light period (nonactive phase) than in the dark period (+24% versus +11% on stress day 3, light versus dark). The results suggest that a stress delivered during the nonactive phase represents a higher cardiovascular risk.
Role of Cyclooxygenase-2 in the Prolonged Regulation of Renal Function
Authors: Roig Francisco , Llinás Maria T. , López Ruth , Salazar F. Javier
Published: October 2002

The role of cyclooxygenase-2 (COX-2) in the prolonged regulation of renal function was evaluated during changes in sodium intake and reduction of NO synthesis. It was evaluated in conscious dogs by administering a selective inhibitor (nimesulide) during 8 consecutive days. Nimesulide administration to dogs with normal or high sodium load did not modify glomerular filtration rate but reduced renal blood flow (16%;
P
<0.05). The vasoconstriction elicited by COX-2 inhibition was greater when NO production was inhibited because glomerular filtration rate decreased by >25% when nimesulide was administered to dogs with a reduced NO synthesis. During low sodium intake, COX-2 inhibition elicited a decrease (
P
<0.05) of both glomerular filtration rate (34%) and renal blood flow (31%). Sodium excretion only decreased (
P
<0.05) during the first day of COX-2 inhibition in dogs with normal or high sodium load. The increase in plasma potassium levels elicited by COX-2 inhibition was greater in dogs with low sodium intake and was enhanced when NO production was inhibited. This change in potassium was not secondary to a decrease in plasma aldosterone levels. The results of this study suggest that COX-2–derived metabolites (1) play a more important role in the long-term regulation of renal hemodynamic when sodium intake is low, (2) protect the renal vasculature from the vasoconstriction secondary to a reduction in NO, (3) are only acutely involved in regulating urinary sodium excretion, and (4) play a more important role in regulating plasma potassium concentration when NO synthesis is reduced.
Essential Role of AT
1A
Receptor in the Development of 2K1C Hypertension
Authors: Červenka Luděk , Horáček Vladislav , Vaněčková Ivana , Hubáček Jaroslav A. , Oliverio Michael I. , Coffman Thomas M. , Navar L. Gabriel
Published: October 2002

The aims of this study were to delineate the relative contribution of angiotensin II (ANG II) subtype 1A (AT
1A
) and 1B (AT
1B
) receptors to the development of two-kidney, one-clip (2K1C) Goldblatt hypertension in mice, to examine if increased nitric oxide synthase (NOS) activity counteracts the vasoconstrictor influences of ANG II in 2K1C hypertensive mice, and to determine the role of ANG II type 2 (AT
2
) receptors in 2K1C hypertension in mice. AT
1A
ANG II receptor knockout (AT
1A
−/−) and wild-type (AT
1A
+/+) mice underwent clipping of the right renal artery. Systolic blood pressure (SBP) was significantly lower in AT
1A
−/− compared with AT
1A
+/+ mice, and neither clip placement nor AT
2
receptor blockade with PD 123319 (PD) altered SBP in AT
1A
−/− mice. A significant and sustained rise in SBP from 119±5 to 163±6 mm Hg was observed in the 2K1C AT
1A
+/+ mice from day 10 to day 26. Chronic PD infusion did not alter the course of hypertension in 2K1C/AT
1A
+/+. Acute PD infusion did not alter mean arterial pressure (MAP) in AT
1A
+/+, PD/AT
1A
+/+, 2K1C/AT
1A
+/+, PD/2K1C/AT
1A
+/+, AT
1A
−/−, PD/AT
1A
−/−, and PD/2K1C/AT
1A
−/− mice compared with basal levels. In contrast, acute PD infusion caused significant increases in MAP in 2K1C/AT
1A
−/− mice. The subsequent acute NOS inhibition caused greater increases in MAP in 2K1C/AT
1A
+/+ and PD/2K1C/AT
1A
+/+ mice than in AT
1A
+/+ and PD/AT
1A
+/+ mice. These results support the essential role of AT
1A
receptors in mediating 2K1C hypertension and support the hypothesis that augmented NO production serves as a counteracting system in this model of hypertension.
NAD(P)H Oxidase Inhibition Improves Endothelial Function in Rat and Human Blood Vessels
Authors: Hamilton Carlene A. , Brosnan M. Julia , Al-Benna Sammy , Berg Geoffrey , Dominiczak Anna F.
Published: October 2002

The NO/superoxide (O
2
−
) balance is a key regulator of endothelial function. O
2
−
levels are elevated in many forms of cardiovascular disease; therefore, decreasing O
2
−
should improve endothelial function. To explore this hypothesis, internal mammary arteries and saphenous veins, obtained from patients undergoing coronary artery revascularization, and aortic and carotid arteries from Wistar-Kyoto and spontaneously hypertensive stroke-prone rats were incubated with O
2
−
dismutase or NAD(P)H oxidase inhibitors. O
2
−
levels were measured using lucigenin chemiluminescence; NO bioavailability was assessed in organ chambers; and mRNA expression of NAD(P)H oxidase components was quantified by use of a Light Cycler. In rat arteries, phenylarsine oxide, 4-(2-aminoethyl)-benzenesulfanyl fluoride, and apocynin all decreased NADH-stimulated O
2
−
production, but only apocynin increased NO bioavailability. In human internal mammary arteries and saphenous veins, apocynin decreased NAD(P)H-stimulated O
2
−
generation and caused vasorelaxation that was endothelium dependent and reversed on addition of the NO synthase inhibitor N
G
-nitro-
l
-arginine methyl ester. In addition, it increased NO production from cultured human endothelial saphenous vein cells. Polyethylene-glycolated O
2
−
dismutase also increased NO bioavailability in rat carotid arteries and human blood vessels, but the effects were smaller than those observed with apocynin. NADH-generated O
2
−
and mRNA expression of p22
phox
, gp91
phox
, and nox-1 were comparable between the 2 strains of rat. This is the first study to demonstrate pharmacological effects of apocynin in human blood vessels. The increases in NO bioavailability shown here suggest that the NAD(P)H oxidase pathway may be a novel target for drug intervention in cardiovascular disease.
Genomic Association/Linkage of Sodium Lithium Countertransport in CEPH Pedigrees
Authors: Schork Nicholas J. , Gardner Jeffrey P. , Zhang Li , Fallin Danielle , Thiel Bonnie , Jakubowski Hieronim , Aviv Abraham
Published: October 2002

Little is known about genetic determinants explaining variation in the erythrocyte sodium-lithium countertransport (SLC), an intermediate phenotype of essential hypertension. We characterized the SLC in immortalized lymphoblasts and showed that its behavior is similar to that of erythrocyte SLC. We then performed association and linkage analyses of the SLC in immortalized lymphoblasts from 5 large pedigrees from the Center d’Etude du Polymorphisme Humain (CEPH) genomics repository. The results of these analyses showed that a number of genomic regions harboring genes involved in glutathione metabolism might explain variations in SLC activity. These findings support evidence that thiol groups play a central role in SLC activity.
Endoglin Upregulation During Experimental Renal Interstitial Fibrosis in Mice
Authors: Rodríguez-Peña Ana , Eleno Nélida , Düwell Anette , Arévalo Miguel , Pérez-Barriocanal Fernando , Flores Olga , Docherty Neil , Bernabeu Carmelo , Letarte Michelle , López-Novoa José M.
Published: October 2002

The goal of the present study was to evaluate the role of endoglin, a transforming growth factor-β1 (TGF-β1) accessory receptor, in the pathogenesis of renal fibrosis. This was achieved by testing a model of tubulo-interstitial fibrosis induced by unilateral ureteral obstruction in endoglin heterozygous (
Eng
+/−
) mice. Northern and Western blot analysis revealed that endoglin expression in kidneys of these mice was significantly reduced compared with
Eng
+/+
littermates. Pronounced interstitial fibrosis induced by ureteral obstruction was confirmed histologically by Masson’s trichromic staining and by increased immunostaining for fibronectin and laminin without significant differences between
Eng
+/−
and
Eng
+/+
mice. Ureteral obstruction induced significant increases in α2(I) and α1(IV) collagen, fibronectin, and TGF-β1 mRNA levels, as well as in total kidney collagen but changes were similar in
Eng
+/−
and
Eng
+/+
mouse kidneys. Ureteral obstruction also induced a 2-fold increase in endoglin mRNA levels in both
Eng
+/+
mice and
Eng
+/−
mice, which was confirmed by Western blot analysis. Thus, the present study provides clear evidence that endoglin is upregulated in the kidneys of mice with interstitial fibrosis induced by unilateral ureteral ligation. However,
Eng
+/−
mice do not show any changes in the severity of renal disease induced in this model when compared with normal mice, suggesting that the absolute level of endoglin is not critical for the effects of TGF-β1 in the renal fibrosis process.
Involvement of Extracellular Signal-Regulated Kinases 1/2 in Cardiac Hypertrophy and Cell Death
Authors: Bueno Orlando F. , Molkentin Jeffery D.
Published: October 2002

In response to pathophysiological stress, the adult heart undergoes hypertrophic enlargement characterized by an increase in the cross-sectional area of individual myofibers. Although cardiac hypertrophy is initially a compensatory response, sustained hypertrophy is a leading predictor for the development of heart failure. At the molecular level, disease-related stimuli invoke endocrine, paracrine, and autocrine regulatory circuits, which directly influence cardiomyocyte hypertrophy, in part, through membrane bound G protein–coupled receptors and receptor tyrosine kinases. These membrane receptors activate intermediate signal transduction pathways within the cytoplasm such as mitogen-activated protein kinases (MAPKs), protein kinase C (PKC), and calcineurin, which directly modify transcriptional regulatory factors promoting alterations in cardiac gene expression. This review will weigh an increasing body of literature implicating the intermediate signaling pathway consisting of MEK1 and extracellular signal-regulated kinases (ERK1/2) as important regulators of cardiac hypertrophy and myocyte survival. The MEK1-ERK1/2 pathway likely occupies a central regulatory position in the signaling hierarchy of a cardiac myocyte given its unique ability to respond to virtually every characterized hypertrophic agonist and stress stimuli examined to date and based on its ability to promote myocyte growth in vitro and in vivo.
Smad2 Mediates Transforming Growth Factor-β Induction of Endothelial Nitric Oxide Synthase Expression
Authors: Saura Marta , Zaragoza Carlos , Cao Wangsen , Bao Clare , Rodríguez-Puyol Manuel , Rodríguez-Puyol Diego , Lowenstein Charles J.
Published: October 2002

Transforming growth factor-β (TGF-β) increases expression of endothelial nitric oxide synthase (eNOS), although the precise mechanism by which it does so is unclear. We report that Smad2, a transcription factor activated by TGF-β, mediates TGF-β induction of eNOS in endothelial cells. TGF-β induces Smad2 translocation from cytoplasm to nucleus, where it directly interacts with a specific region of the eNOS promoter. Overexpression of Smad2 increases basal levels of eNOS, and further increases TGF-β stimulation of eNOS expression. Ectopic expression of Smurf, an antagonizer of Smad2, decreases Smad2 expression and blocks TGF-β induction of eNOS. Because Smad2 can interact with a variety of transcription factors, coactivators, and corepressors, Smad2 may thus act as an integrator of multiple signals in the regulation of eNOS expression.
Comparison of Tibolone and Conjugated Equine Estrogens Effects on Carotid Artery Atherosclerosis of Postmenopausal Monkeys
Authors: Clarkson Thomas B. , Anthony Mary S. , Mikkola Tomi S. , St Clair Richard W.
Published: October 2002

Background and Purpose—

Tibolone is a tissue-specific compound that has favorable effects on bone and menopausal symptoms without stimulating endometrium or breast, but lowers concentrations of plasma high-density lipoprotein (HDL) cholesterol (HDLC). This study was designed to determine whether the HDL lowering with tibolone exacerbated common or internal carotid artery atherosclerosis and to evaluate tibolone treatment relative to conjugated equine estrogens (CEE) alone or in combination with medroxyprogesterone acetate (MPA).

Methods—

Carotid artery atherosclerosis was compared in groups of surgically postmenopausal cynomolgus monkeys treated with CEE, CEE+MPA, or either of 2 doses of tibolone versus untreated monkeys.

Results—

Despite a 30% to 52% lowering of HDLC with tibolone, there was no significant effect on carotid artery atherosclerosis. CEE and CEE+MPA, however, inhibited carotid artery atherosclerosis by ≈60%.

Conclusions—

In surgically postmenopausal cynomolgus monkeys, CEE and CEE+MPA inhibited common and internal carotid artery atherosclerosis. Despite the potentially adverse effects of tibolone on HDLC, tibolone did not exacerbate atherosclerosis.
Blood-Brain Barrier Disruption and Matrix Metalloproteinase-9 Expression During Reperfusion Injury
Authors: Aoki Toshiaki , Sumii Toshihisa , Mori Tatsuro , Wang Xiaoying , Lo Eng H.
Published: October 2002

Background and Purpose—

Most experimental models of cerebral ischemia use mechanical methods of occlusion and reperfusion. However, differences between mechanical reperfusion versus clot thrombolysis may influence reperfusion injury profiles. In this study we compared blood flow recovery, blood-brain barrier (BBB) permeability, and matrix metalloproteinase-9 (MMP-9) expression in cortex after mechanical versus thrombolytic reperfusion in rat focal ischemia.

Methods—

Male spontaneously hypertensive rats were used. Mechanical ischemia/reperfusion was achieved with the use of an intraluminal filament to occlude the middle cerebral artery for 2 hours. Thrombolytic reperfusion was achieved by administering tissue plasminogen activator at 2 hours after embolic focal ischemia. Regional cortical blood flow was monitored by laser-Doppler flowmetry. BBB permeability in cortex was measured by Evans blue dye leakage. Cortical MMP-9 levels were assessed with zymography and immunohistochemistry.

Results—

Blood flow recovery during mechanical reperfusion was complete in both central and peripheral areas of ischemic cortex. However, after thrombolysis, reperfusion was incomplete, with moderate recovery in the periphery only. BBB permeability was mainly increased in the central regions of the ischemic cortex after mechanical reperfusion but was increased in both central and peripheral areas after thrombolysis. Overall, MMP-9 levels were higher after embolic versus mechanical ischemia/reperfusion, even though ischemic injury was similar in both models at 24 hours.

Conclusions—

There are significant differences in the profiles of blood flow recovery, BBB leakage, and MMP-9 upregulation in mechanical versus thrombolytic reperfusion after focal ischemia.
Evaluation of Proxy Responses to the Stroke Impact Scale
Authors: Duncan Pamela W. , Lai Sue Min , Tyler Denise , Perera Subashan , Reker Dean M. , Studenski Stephanie
Published: October 2002

Background and Purpose—

The purposes of this study were to compare proxy-patient responses on each domain of the Stroke Impact Scale (SIS) and the SIS-16, estimate the bias, and evaluate the validity of proxy scores.

Methods—

Two hundred eighty-seven patient and proxy pairs from the Kansas City Stroke Registry participated in the study. All patients were assessed in their home or nursing facility between 90 and 120 days after stroke with the use of the modified Rankin Scale Motricity Index (strength), Barthel Index (activities of daily living), Lawton assessment (instrumental activities of daily living), Folstein Mini-Mental State Examination (cognition), and the SIS. Eligible proxies were individuals who were aged ≥18 years, had known the patient for at least 1 year, and saw the patient at least once each week. All proxy interviews were conducted within 7 days of (before or after) the patient’s interview.

Results—

Three hundred seventy-seven patients from the Kansas City Stroke Registry were eligible for the study. Seventy-seven patients or proxies refused participation. Thirteen patients of the consenting patient-proxy pairs were too aphasic or cognitively impaired to complete the interviews and were dropped from the study. Proxies scored patients as more severely affected than patients scored themselves on the SIS-16 and in 7 of 8 domains of the full SIS (5 were statistically significant at α=0.05). The proxy bias toward overrating the severity of the patient’s condition tended to increase as the severity of the stroke increased. However, the magnitude of the biases between patient and proxy means, as measured by effect size, was small (range, −0.1 to 0.4). The strength of the agreement, as measured by intraclass correlation coefficients, between proxy and patient ranged from 0.50 to 0.83. Agreement was best for the observable physical domains. Both patient and proxy scores in all domains were significantly different across Rankin categories. Concurrent validity for both patient and proxy correlations with the Folstein Mini-Mental State Examination, Barthel Index, Lawton instrumental activities of daily living, and Motricity Index was good to excellent (range, 0.37 to 0.78).

Conclusions—

Proxies provide valid information for assessment of stroke outcomes. There are significant differences between patient and proxy reporting on SIS domains and the SIS-16. However, the observed biases are small and not clinically meaningful.
Leukocyte Count Is Associated With Aortic Arch Plaque Thickness
Authors: Elkind Mitchell S.V. , Sciacca Robert , Boden-Albala Bernadette , Homma Shunichi , Di Tullio Marco R.
Published: October 2002

Background and Purpose—

Leukocyte count has been associated with cardiovascular and cerebrovascular disease, including carotid plaque thickness, in several studies. We hypothesized that white blood cell count is associated with aortic arch plaque thickness (AAPT).

Methods—

Leukocyte count was measured in randomly selected stroke-free community participants undergoing transesophageal echocardiography. AAPT was measured for each subject and dichotomized into <4 and ≥4 mm (thick plaque). Multivariate linear and logistic regression was used to calculate the effect of leukocyte count on AAPT after adjustment for potential confounding factors. Mean age of the 145 participants was 68.5±8.3 years; 43.5% were women; 15.9% were white; 31.7% were black; and 49.0% were Hispanic.

Results—

Mean leukocyte count was 5.88±1.76×10
9
/L. Each unit increase in leukocyte count was associated with a mean 0.28-mm increase in AAPT (
P
=0.0036). After adjustment for other atherosclerosis risk factors, including age, sex, hypertension, diabetes, hyperlipidemia, and smoking, the relationship persisted (mean increase in AAPT, 0.24 mm;
P
=0.0064). Thirty-five participants (24.1%) had AAPT ≥4 mm. Mean leukocyte count among those with thick plaque was significantly higher than among those with plaque <4 mm (6.54±1.60 versus 5.65±1.76×10
9
/L, respectively;
P
=0.009). Each unit increase in leukocyte count was associated with an increased risk of thick plaque (adjusted odds ratio, 1.38; 95% CI, 1.05 to 1.79). The relationships were similar for men and women and for those <70 or ≥70 years of age.

Conclusions—

Leukocyte count is associated with AAPT and is specifically correlated with AAPT ≥4 mm, a degree of thickening associated with increased stroke risk. These findings are consistent with current hypotheses regarding the inflammatory or infectious etiology of risk of atherosclerosis and stroke.
Endovascular Treatment of Ruptured Intracranial Aneurysms in Patients Aged 65 Years and Older
Authors: Sedat J. , Dib M. , Lonjon M. , Litrico S. , Von Langsdorf D. , Fontaine D. , Paquis P.
Published: October 2002

Background and Purpose—

We sought to describe the clinical outcome and results obtained in the endovascular therapy of ruptured cerebral aneurysms in the elderly over an 8-year period. We compared endovascular therapy results in patients aged ≥65 and <65 years.

Methods—

During 1993–1999, 52 patients aged 65 to 85 years (mean age, 71.5±4.7 years) were embolized with the use of Guglielmi detachable coils (group I). During the same period, 143 patients aged <65 years (mean age, 47±11 years) with ruptured cerebral aneurysm were treated with the same technique (group II). A clinical assessment was made on admission with the Hunt and Hess (HH) classification and again in the 12th month with the Glasgow Outcome Scale (GOS), with arteriographic control in months 3 and 12.

Results—

In group I, clinical grades on admission were as follows: HH 1, 9.5%; HH 2, 33%; HH 3, 21%; HH 4, 34.5%; HH 5, 2%. Outcome was favorable in 48% of patients (GOS 1 or 2); the mortality rate was 23%. No rebleeding was observed. Patients presenting lesions ≥10 mm had an unfavorable outcome in >77% of cases. Thromboembolic complications were present in 13% of cases. In group II, clinical grades on admission were as follows: HH 1, 14.5%; HH 2, 47%; HH 3, 11%; HH 4, 24%; HH 5, 3.5%. Favorable outcome (GOS 1 or 2) was observed in 77% of cases, with 14% mortality. Complications due to the endovascular procedure were present in 4.2% of cases. Patients with HH grades 1 or 2 on admission showed a positive outcome (GOS 1 or 2) in 77% of cases in group I and in 88.5% of cases in group II. Mortality was 9% in the first subgroup compared with 2.8% in the second. Patients who had a high clinical grade on admission (HH 4 or 5) showed a favorable outcome (GOS 1 or 2) in 16% of cases in group I compared with 41% in group II.

Conclusions—

Endovascular treatment of ruptured intracranial aneurysms in patients aged ≥65 years appears to be effective against rebleeding and represents an alternative to surgery. However, perioperative thromboembolic complications are more frequent in the elderly population.
Relative Edema Volume Is a Predictor of Outcome in Patients With Hyperacute Spontaneous Intracerebral Hemorrhage
Authors: Gebel James M. , Jauch Edward C. , Brott Thomas G. , Khoury Jane , Sauerbeck Laura , Salisbury Shelia , Spilker Judith , Tomsick Thomas A. , Duldner John , Broderick Joseph P.
Published: October 2002

Background and Purpose—

Little is known about the relationship between perihematomal edema in spontaneous intracerebral hemorrhage (ICH) and outcome. The purpose of this study was to determine whether absolute or relative edema volume (edema volume divided by hematoma volume) predicts mortality or functional outcome in patients with hyperacute spontaneous ICH. We hypothesized that increasing baseline relative edema volume is associated with greater probability of poor functional outcome.

Methods—

This was a secondary analysis of a prospective, population-based study of hematoma growth in 142 patients with spontaneous ICH. Patients were imaged within 3 hours of onset, then 1 and 20 hours later. Our primary analysis excluded patients with anticoagulant use (n=7), underlying aneurysm/vascular malformation (n=9), trauma (n=1), incomplete data (n=20), infratentorial ICH (n=17), intraventricular extension (n=38), and no consent (n=2). We analyzed whether associations existed between baseline edema volumes or other clinical/radiological variables and either 12-week modified Rankin Scale score >2 or 30-day mortality. Secondary analyses used 20-hour CT scan data, all patients with supratentorial ICH, and 12-week Barthel Index score <85.

Results—

By multivariable logistic regression analysis, baseline relative edema was the strongest independent predictor of functional outcome and was associated with lesser odds of poor 3-month functional outcome (odds ratio, 0.09 per 1.0-unit [100%] increase; 95% CI, 0.01 to 0.64;
P
=0.016) and 12-week Barthel Index score <85 (odds ratio, 0.12; 95% CI, 0.02 to 0.91;
P
=0.039) but did not predict mortality. Secondary analyses confirmed this result. Absolute edema volume predicted neither mortality nor functional outcome.

Conclusions—

Relative edema is strongly predictive of functional outcome in patients with hyperacute supratentorial spontaneous ICH without intraventricular extension.
Characterization of Incident Stroke Signs and Symptoms
Authors: Rathore Saif S. , Hinn Albert R. , Cooper Lawton S. , Tyroler Herman A. , Rosamond Wayne D.
Published: October 2002

Background and Purpose—

Although patterns of stroke occurrence and mortality have been well studied, few epidemiological data are available regarding the clinical characteristics of stroke events.

Methods—

We evaluated hospitalized stroke events reported in the Atherosclerosis Risk in Communities (ARIC) Study to describe the clinical characteristics of incident stroke. Confirmed stroke cases (n=474) were evaluated for stroke symptoms (headache, vertigo, gait disturbance, convulsions) and stroke signs (hemianopia, diplopia, speech deficits, paresis, paresthesia/sensory deficits) and their univariate associations with race, sex, and stroke subtype.

Results—

Over 9.2 years of follow-up, 402 (85%) ischemic and 72 (15%) hemorrhagic strokes occurred. Frequency of stroke symptoms (95% CIs) were as follows: headache (27.4%; 23.4% to 31.4%), gait disturbance (10.8%; 7.9% to 13.6%), convulsions (4.4%; 2.6% to 6.3%), and vertigo (2.1%; 0.8% to 3.4%). Speech deficits occurred in 24.0% (20.2% to 27.9%), hemianopia in 14.6% (11.4% to 17.7%), and diplopia in 5.5% (3.4% to 7.5%) of cases. Most cases involved paresis (81.6%; 78.1% to 85.1%), while fewer cases experienced sensory deficits (44.5%; 40.0% to 49.0%). Blacks were more likely than whites to experience paresis (85.4% versus 78.2%;
P
=0.044). Men were more likely than women to experience a gait disturbance (14.4% versus 6.7%;
P
=0.007). Persons with hemorrhagic strokes had a higher proportion of headaches (55.6% versus 22.4%;
P
=0.001) and convulsions (11.1% versus 3.2%;
P
=0.003) than those with ischemic events, while speech and sensory deficits were more common in ischemic strokes (26.1% versus 12.5%,
P
=0.013, and 49.0% versus 19.4%,
P
=0.001, respectively).

Conclusions—

We present epidemiological data concerning the clinical characteristics of incident stroke in a population-based cohort. Although minor differences by race, sex, and stroke subtype were observed, data from additional follow-up are required to confirm observed variations.
Does Acupuncture Improve Motor Recovery After Stroke?
Authors: Sze Frank Kai-hoi , Wong Eric , Or Kevin K.H. , Lau Joseph , Woo Jean
Published: October 2002

Background and Purpose—

Acupuncture may be a promising treatment for poststroke paralysis. We conducted a meta-analysis, assessing the efficacy of acupuncture with and without stroke rehabilitation.

Methods—

We identified randomized trials comparing acupuncture with no acupuncture within 6 months of stroke by searching MEDLINE, CINAHL, EMBASE, Cochrane Library, and Chinese medical literature databases. Two reviewers independently extracted data on study characteristics, patient characteristics, and impairment and disability outcomes. The outcome measures were internationally recognized or nationally approved. The fixed- and random-effects models were used to combine effect size and odds ratio across studies.

Results—

Fourteen trials with 1213 patients met all the inclusion criteria. For the comparison of acupuncture with no acupuncture in addition to stroke rehabilitation, the pooled random-effects estimates of the change in motor impairment and disability were 0.06 (95% CI, −0.12 to 0.24) and 0.49 (95% CI, 0.03 to 0.96), respectively, with heterogeneity in disability measures (
P
=0.05, χ
2
test). For the comparison of real with sham acupuncture, the pooled random-effects estimate of the change in disability was 0.07 (95% CI, −0.34 to 0.48). For the comparison of acupuncture with no acupuncture without stroke rehabilitation, the pooled random-effects estimate of the change in motor impairment was 0.46 (95% CI, −0.20 to 1.12), and the pooled random-effects odds ratio for disability was 12.5 (95% CI, 4.3 to 36.2), with no statistically significant heterogeneity (
P
=0.97 and
P
=0.12, respectively, χ
2
test), but the study quality was poor.

Conclusions—

This meta-analysis suggests that with stroke rehabilitation, acupuncture has no additional effect on motor recovery but has a small positive effect on disability, which may be due to a true placebo effect and varied study quality. The efficacy of acupuncture without stroke rehabilitation remains uncertain, mainly because of the poor quality of such studies.
Electroencephalographic Activity in a Flanker Interference Task Using Japanese Orthography
Authors: Yamaguchi Shuhei , Toyoda Genya , Xu Jiang , Kobayashi Shotai , Henik Avishai
Published: October 2002

The neural activities for color word interference effects were investigated using event-related brain potentials (ERPs) recorded in a flanker-type interference task. Kanji words (Japanese morphograms) and kana words (Japanese phono-grams) were used as the flanker stimuli to obtain insights about hemispheric specialization for processing two types of Japanese orthographies. Interference effects in reaction time were larger when kanji words were presented in the left visual field and when kana words were in the right visual field. ERPs were modulated by the incongruent flankers, which generated a negative ERP component with the different onset and offset depending on flanker attributes. Consistent with the behavioral data, the interference-related negativity was observed for kanji words presented in the left visual field and for kana words in the right visual field. The negativity distributed maximally over the fronto-central site. The early part of the negativity distributed strongly over the frontal midline area, whereas it extended bilaterally over the frontal area in the late phase. The present results support the view of preferential processing of kanji in the right hemisphere and that of kana in the left hemisphere. The temporal profile of scalp topographies for the interference-related neural activity suggests that the medial and dorsolateral prefrontal regions may be involved in maintaining attentional set and conflict resolution.
Electrophysiological Measures of Language Processing in Bilinguals
Authors: Proverbio Alice Mado , Čok Barbara , Zani Alberto
Published: October 2002

The aim of the present study was to investigate how multiple languages are represented in the human brain. Event-related brain potentials (ERPs) were recorded from right-handed polyglots and monolinguals during a task involving silent reading. The participants in the experiment were nine Italian monolinguals and nine Italian/Slovenian bilinguals of a Slovenian minority in Trieste; the bilinguals, highly fluent in both languages, had spoken both languages since birth. The stimuli were terminal words that would correctly complete a short, meaningful, previously shown sentence, or else were semantically or syntactically incorrect. The task consisted in deciding whether the sentences were well formed or not, giving the response by pressing a button. Both groups read the same set of 200 Italian sentences to compare the linguistic processing, while the bilinguals also received a set of 200 Slovenian sentences, comparable in complexity and length, to compare the processing of the two languages within the group. For the bilinguals, the ERP results revealed a strong, left-sided activation, reflected by the N1 component, of the occipito-temporal regions dedicated to orthographic processing, with a latency of about 150 msec for Slovenian words, but bilateral activation of the same areas for Italian words, which was also displayed by topographical mapping. In monolinguals, semantic error produced a long-lasting negative response (N2 and N4) that was greater over the right hemisphere, whereas syntactic error activated mostly the left hemisphere. Conversely, in the bilinguals, semantic incongruence resulted in greater response over the left hemisphere than over the right. In this group, the P615 syntactical error responses were of equal amplitude on both hemispheres for Italian words and greater on the right side for Slovenian words.

The present findings support the view that there are inter- and intrahemispheric brain activation asymmetries when monolingual and bilingual speakers comprehend written language. The fact that the bilingual speakers in the present study were highly fluent and had acquired both languages in early infancy suggests that the brain activation patterns do not depend on the age of acquisition or the fluency level, as in the case of late, not-so-proficient L2 language learners, but on the functional organization of the bilinguals' brain due to polyglotism and based on brain plasticity.
Auditory Peripersonal Space in Humans
Authors: Farnè Alessandro , Làdavas Elisabetta
Published: October 2002

In the present study we report neuropsychological evidence of the existence of an auditory peripersonal space representation around the head in humans and its characteristics. In a group of right brain-damaged patients with tactile extinction, we found that a sound delivered near the ipsilesional side of the head (20 cm) strongly extinguished a tactile stimulus delivered to the contralesional side of the head (cross-modal auditory-tactile extinction). By contrast, when an auditory stimulus was presented far from the head (70 cm), cross-modal extinction was dramatically reduced. This spatially specific cross-modal extinction was most consistently found (i.e., both in the front and back spaces) when a complex sound was presented, like a white noise burst. Pure tones produced spatially specific cross-modal extinction when presented in the back space, but not in the front space. In addition, the most severe cross-modal extinction emerged when sounds came from behind the head, thus showing that the back space is more sensitive than the front space to the sensory interaction of auditory-tactile inputs. Finally, when cross-modal effects were investigated by reversing the spatial arrangement of cross-modal stimuli (i.e., touch on the right and sound on the left), we found that an ipsilesional tactile stimulus, although inducing a small amount of cross-modal tactile-auditory extinction, did not produce any spatial-specific effect. Therefore, the selective aspects of cross-modal interaction found near the head cannot be explained by a competition between a damaged left spatial representation and an intact right spatial representation. Thus, consistent with neurophysiological evidence from monkeys, our findings strongly support the existence, in humans, of an integrated cross-modal system coding auditory and tactile stimuli near the body, that is, in the peripersonal space.
THE PERSONAL IS POLITICAL: COVENANTAL AND AFFECTIONATE LOVE ('ĀHĒB, 'AHĂBÂ) IN THE HEBREW BIBLE
Authors: Ackerman Susan
Published: October 2002

This paper explores points of connection between texts describing Yahweh's covenantal love for Israel and texts concerning the interpersonal loving relationships of men and women and parents and children. Although these covenantal and interpersonal relationships are to be distinguished in many ways, they do hold certain features in common: both are construed in a way that is very one-sided, and, in both, it is typically
SOME HEBREW MISREADINGS IN THE SEPTUAGINT OF AMOS
Authors: Gelston
Published: October 2002

One of the many different possible reasons for variations between the MT and the LXX is misreading of the Hebrew text by the LXX translator. Such misreading often extends to only one or two letters, and provides a ready explanation for renderings otherwise difficult to understand. There is an unusual concentration of such apparent misreadings in the LXX of Amos, 23 particular cases being briefly examined and classified in this communication. Three cases are of more than usual interest and are examined in greater detail. The cumulative effect of the occurence of a number of probable cases of misreading in a comparatively short text, where the translation of the LXX is generally accurate, is most probably to be explained by indistinct writing or damage to the Hebrew Vorlage of the LXX translator.