bluuebunny/crossref_metadata_2025 huggingface dataset:
Positional Identification of Hypertension Susceptibility Genes on Chromosome 2
Authors: Barkley Ruth Ann , Chakravarti Aravinda , Cooper Richard S. , Ellison R. Curtis , Hunt Steven C. , Province Michael A. , Turner Stephen T. , Weder Alan B. , Boerwinkle Eric
Published: January 2004

Chromosome 2 has been consistently identified as a genomic region with genetic linkage evidence suggesting that one or more loci contributes to blood pressure and hypertension status. As with all complex disease traits, following-up linkage evidence to identify the underlying susceptibility gene(s) is an arduous yet biologically and clinically important task. Using combined positional candidate gene methods, the Family Blood Pressure Program (FBPP) has concentrated efforts in narrowing a large region of chromosome 2, demonstrating evidence for linkage in several populations, and identifying underlying candidate hypertension susceptibility gene(s). Initial informatics efforts identified the boundaries of the region and the known genes within it. A total of 82 polymorphic sites in 8 genes were genotyped in a large hypothesis-generating sample consisting of 1640 African Americans, 1339 whites, and 1616 Mexican Americans. After resampling-based false discovery adjustment,
SLC4A5
, a sodium bicarbonate transporter, was identified as a primary candidate gene for hypertension. Polymorphisms in
SLC4A5
were subsequently genotyped and analyzed for validation in two other subcomponents of the FBPP, each contributing African Americans (N=461; N=778) and whites (N=550; N=967). Again, single nucleotide polymorphisms within this gene were significantly associated with blood pressure levels and hypertension status. Although not identifying a single causal gene variant that is significantly associated with blood pressure levels and hypertension status across all samples, the results further implicate
SLC4A5
as a candidate hypertension susceptibility gene. Moreover, the present study validates previous evidence for one or more genes on chromosome 2 that influence hypertension-related phenotypes in the population-at-large.
Endogenous Angiotensin and Pressure Modulate Brain Angiotensinogen and AT
1A
mRNA Expression
Authors: Sangaleti Carine T. , Crescenzi Alessandra , Michelini Lisete C.
Published: January 2004

In the coarctation hypertension model, we showed both dissociation of plasma renin activity from cardiovascular-induced effects and the reversal of hypertension-induced responses by losartan. In this study, we investigated the effects of hypertension on the expression of brain renin-angiotensin system components and the simultaneous functional responses and effects of long-term angiotensin II (AT) receptor blockade on these responses. Rats were given vehicle or losartan for 9 days and subjected to subdiaphragmatic aortic constriction or sham surgery after 4 days of treatment. On the fifth postsurgical day, pressure and heart rate were measured in the conscious state; the brain was perfused and removed afterward. Sequential slices of brainstem were hybridized with
35
S-oligodeoxynucleotide probes for angiotensinogen, AT
1A
, and AT
1B
receptors and processed for autoradiography and densitometry. In vehicle-treated rats, hypertension was accompanied by tachycardia and marked increments in angiotensinogen and AT
1A
mRNA expression in the cardiovascular system–controlling brainstem areas. In the nucleus tractus solitarii, AT
1A
density was correlated with both pressure and heart rate values (
P
<0.01), whereas angiotensinogen levels were correlated with pressure only (
P
<0.05). Losartan did not change the pressure of hypertensive rats (142±4 versus 146±2 mm Hg, losartan versus vehicle) and the hypertension-induced angiotensinogen mRNA expression but did block both tachycardic response and hypertension-induced AT
1A
mRNA expression. Hypertension and losartan did not change AT
1B
mRNA expression. The hypertension-induced positive feedback on angiotensinogen and AT
1A
mRNA expression supports the concept of a permissive role for brain angiotensin II in orchestrating circulatory responses during the development of hypertension. These data also explain the efficacy of long-term AT
1
receptor blockade to reverse hypertension-induced effects.
Short Telomeres Are Associated With Increased Carotid Atherosclerosis in Hypertensive Subjects
Authors: Benetos Athanase , Gardner Jeffrey P. , Zureik Mahmoud , Labat Carlos , Xiaobin Lu , Adamopoulos Chris , Temmar Mohamed , Bean Kathryn E. , Thomas Frédérique , Aviv Abraham
Published: January 2004

Recent studies have shown that individuals with shorter telomeres present a higher prevalence of arterial lesions and higher risk of cardiovascular disease mortality. As a group, patients with high blood pressure are at an increased risk for cardiovascular diseases. However, some hypertensive patients are more prone than others to atherosclerotic lesions. The main objective of this study was to examine the relationship between telomere length, as expressed in white blood cells, and carotid artery atherosclerotic plaques in hypertensive males. Data from 163 treated hypertensive men who were volunteers for a free medical examination were analyzed. Extracranial carotid plaques were assessed with B-mode ultrasound. Telomere length was measured from DNA samples extracted from white blood cells. The results of this study show that telomere length was shorter in hypertensive men with carotid artery plaques versus hypertensive men without plaques (8.17±0.07 kb versus 8.46±0.07 kb;
P
<0.01). Multivariate analysis showed that in addition to age, telomere length was a significant predictor of the presence of carotid artery plaques. The findings from this study suggest that in the presence of chronic hypertension, which is a major risk factor for atherosclerotic lesions, shorter telomere length in white blood cells is associated with an increased predilection to carotid artery atherosclerosis.
Peroxisome Proliferator-Activated Receptor γ: Implications for Cardiovascular Disease
Authors: Hsueh Willa A. , Bruemmer Dennis
Published: January 2004

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. PPARγ is expressed by macrophages, endothelial cells, and vascular smooth muscle cells. It regulates gene expression of key proteins involved in lipid metabolism, vascular inflammation, and proliferation contributing to atherogenesis and postangioplasty restenosis. The discovery of synthetic ligands for PPARγ has led to significant enhancement of our understanding of the mechanism of their ligand-dependent activation and subsequent biological effects, particularly with respect to the role of PPARγ in vascular pathophysiology. The thiazolidinedione PPARγ agonists not only improve insulin resistance in patients with type II diabetes but also exert a broad spectrum of antiatherogenic effects in vitro and in animal models of atherosclerosis. In this review, we summarize the important role of PPARγ as a molecular target for thiazolidinediones and its implications for the control of vascular inflammation and proliferation for the cardiovascular system.
Arterial Stiffness and Kidney Function
Authors: Safar Michel E. , London Gérard M , Plante Gérard E.
Published: January 2004

The vascular hallmark of subjects with end-stage renal disease undergoing hemodialysis is increased aortic stiffness, a phenomenon independent of mean arterial blood pressure, wall stress, and standard cardiovascular risk factors such as plasma glucose, cholesterol, obesity, and smoking. These observations suggest that subtle links might associate arterial stiffness and kidney function in normotensive and hypertensive populations. Recently, aortic pulse wave velocity and creatinine clearance have been shown to be statistically associated in subjects with plasma creatinine ≤130 μmol/L, again independently of mean arterial blood pressure and classical cardiovascular risk factors. This association was even shown to predominate in subjects younger than age 55 years. In addition, acceleration of aortic pulse wave velocity with age was more important in these subjects than in untreated normotensive control individuals, and the phenomenon was consistently predicted by baseline plasma creatinine values. Among all antihypertensive drugs, angiotensin-converting enzyme inhibitors only were shown to exhibit a significant and independent effect on aortic stiffness. The use of these drugs was significantly associated with improvement of large aortic stiffness in subjects treated for hypertension. In conclusion, increased stiffness of central arteries is independently associated with reduced creatinine clearance in subjects with mild to severe renal insufficiency, indicating that kidney diseases may interact not only with small but also with large conduit arteries, independently of age, blood pressure level, and classical cardiovascular risk factors. Whether sodium, divalent ionic species (calcium, phosphates), and the renin-angiotensin-aldosterone system play a role in such alterations remains to be elucidated.
Acromegalic Patients Show the Presence of Hypertrophic Remodeling of Subcutaneous Small Resistance Arteries
Authors: Rizzoni Damiano , Porteri Enzo , Giustina Andrea , De Ciuceis Carolina , Sleiman Intissar , Boari Gianluca E. M. , Castellano Maurizio , Muiesan Maria Lorenza , Bonadonna Stefania , Burattin Anna , Cerudelli Bruno , Agabiti-Rosei Enrico
Published: January 2004

Structural alterations of small resistance arteries in patients with essential hypertension (EH) are mostly characterized by inward eutrophic remodeling. However, we have observed the presence of hypertrophic remodeling in patients with renovascular hypertension, as well as in patients with noninsulin-dependent diabetes mellitus, suggesting a relevant effect of humoral growth factors on vascular structure. Growth hormone may stimulate in vitro proliferation of vascular smooth muscle cells. However, no data are presently available about small artery structure in acromegalic patients. Therefore, we have investigated the structure of subcutaneous small arteries in 12 normotensive (NT) subjects, in 12 EH subjects, and in 9 acromegalic patients (APs). All subjects underwent biopsy of the subcutaneous fat; then, small resistance arteries were dissected and mounted on a micromyograph. The normalized internal diameter, media thickness, media-to-lumen ratio, the media cross-sectional area together with remodeling, and growth indices were calculated. Demographic variables were similar in the three groups, except for blood pressure. The media-to-lumen ratio was significantly greater in EH and AP, compared with NT. No difference was observed between EH and AP. The media cross-sectional area was significantly greater in AP compared with EH and with NT. The calculation of remodeling and growth index suggests the presence of eutrophic remodeling in EH (growth index 0%) and of hypertrophic remodeling in AP (growth index 40%). In conclusion, our data suggest the presence of hypertrophic remodeling of subcutaneous small resistance arteries of AP, probably as a consequence of growth-stimulator properties of IGF-1.
Resistant Hypertension, Obesity, Sleep Apnea, and Aldosterone
Authors: Goodfriend Theodore L. , Calhoun David A.
Published: January 2004

Hypertension resistant to 2 antihypertensive drugs is more common among obese patients than among lean patients. The case we describe and the observations we report suggest that refractoriness among obese hypertensives is frequently caused by obstructive sleep apnea and/or inappropriately high plasma aldosterone levels. In other words, obese hypertensives may have sleep apnea, obese hypertensives without sleep apnea may have inappropriately elevated levels of plasma aldosterone, and a surprising number of obese patients with sleep apnea also have elevated levels of aldosterone. The mechanisms by which obesity and obstructive sleep apnea increase aldosterone levels and raise blood pressure are not understood, but sympathetic nervous system activation and production of nonclassical adrenal stimuli are two possibilities. Obstructive sleep apnea can be detected with a careful history and various sleep studies. Inappropriately elevated aldosterone levels can be detected by measuring the ratio of plasma aldosterone concentration to plasma renin activity. Successful treatment of these resistant hypertensives often can be achieved by devices that provide positive pressure to the upper airway to correct obstructive sleep apnea and by incorporating an aldosterone antagonist in the therapeutic regimen.
Cardiac-Specific Induction of the Transcriptional Coactivator Peroxisome Proliferator-Activated Receptor γ Coactivator-1α Promotes Mitochondrial Biogenesis and Reversible Cardiomyopathy in a Developmental Stage-Dependent Manner
Authors: Russell Laurie K. , Mansfield Carolyn M. , Lehman John J. , Kovacs Attila , Courtois Michael , Saffitz Jeffrey E. , Medeiros Denis M. , Valencik Maria L. , McDonald John A. , Kelly Daniel P.
Published: January 2004

Recent evidence has identified the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) as a regulator of cardiac energy metabolism and mitochondrial biogenesis. We describe the development of a transgenic system that permits inducible, cardiac-specific overexpression of PGC-1α. Expression of the PGC-1α transgene in this system (tet-on PGC-1α) is cardiac-specific in the presence of doxycycline (dox) and is not leaky in the absence of dox. Overexpression of PGC-1α in tet-on PGC-1α mice during the neonatal stages leads to a dramatic increase in cardiac mitochondrial number and size coincident with upregulation of gene markers associated with mitochondrial biogenesis. In contrast, overexpression of PGC-1α in the hearts of adult mice leads to a modest increase in mitochondrial number, derangements of mitochondrial ultrastructure, and development of cardiomyopathy. The cardiomyopathy in adult tet-on PGC-1α mice is characterized by an increase in ventricular mass and chamber dilatation. Surprisingly, removal of dox and cessation of PGC-1α overexpression in adult mice results in complete reversal of cardiac dysfunction within 4 weeks. These results indicate that PGC-1α drives mitochondrial biogenesis in a developmental stage-dependent manner permissive during the neonatal period. This unique murine model should prove useful for the study of the molecular regulatory programs governing mitochondrial biogenesis and characterization of the relationship between mitochondrial dysfunction and cardiomyopathy and as a general model of inducible, reversible cardiomyopathy.
Frequency- and Afterload-Dependent Cardiac Modulation In Vivo by Troponin I With Constitutively Active Protein Kinase A Phosphorylation Sites
Authors: Takimoto Eiki , Soergel David G. , Janssen Paul M.L. , Stull Linda B. , Kass David A. , Murphy Anne M.
Published: January 2004

Acute β-adrenergic stimulation enhances cardiac contractility, accelerates muscle relaxation, and amplifies the inotropic and lusitropic response to increased stimulation frequency. These effects are modulated by phosphorylation of calcium handling and myofilament proteins such as troponin I (TnI) by protein kinase A (PKA). To more directly delineate the role of TnI PKA phosphorylation, transgenic mice were generated that overexpress cardiac TnI in which the serine residues normally targeted by PKA are mutated to aspartic acid to mimic constitutive phosphorylation (TnIDD
22,23
). Native cardiac TnI was near completely replaced in one transgenic line as assessed by in vitro phosphorylation, and this led to reduced calcium sensitivity of myofibrillar MgATPase, as expected. TnIDD
22,23
mice had mildly enhanced basal systolic and diastolic function, and displayed marked augmentation of frequency-dependent inotropy and relaxation, with a peak frequency response 2-fold greater in mutants than controls (
P
<0.005). Increasing afterload prolonged relaxation more in nontransgenic than TnIDD
22,23
(
P
<0.02), whereas contractile responses to afterload were similar between these strains. Isoproterenol treatment eliminated the differential force-frequency and afterload response between TnIDD
22,23
and controls. In contrast to in vivo studies, isolated isometric trabeculae from nontransgenic and TnIDD
22,23
mice had similar basal, isoproterenol-, and frequency-stimulated function, suggesting that muscle shortening may be important to TnI PKA effects. These results support a novel role for cardiac TnI PKA phosphorylation in the rate-dependent enhancement of systolic and diastolic function in vivo and afterload sensitivity of relaxation. These results have implications for cardiac failure in which force-frequency modulation is blunted and afterload relaxation sensitivity increased in association with diminished PKA TnI phosphorylation.
Thalamic Lesions in Vascular Dementia
Authors: Bastos Leite António J. , van Straaten Elisabeth C.W. , Scheltens Philip , Lycklama Geert , Barkhof Frederik
Published: January 2004

Background and Purpose—

The criteria of the National Institute of Neurological Disorders and Stroke (NINDS)–Association Internationale pour la Recherche et l’Enseignement en Neurosciences (AIREN) include thalamic lesions for the diagnosis of vascular dementia (VaD). Although studies concerning VaD and brain aging advocate the use of fluid-attenuated inversion recovery (FLAIR) or T2-weighted images (T2-WI) to detect ischemic lesions, none compared the sensitivity of these sequences to depict thalamic lesions.

Methods—

We performed a blinded review of T2-WI and FLAIR images in 73 patients fulfilling the radiological part of the NINDS-AIREN criteria (mean age, 71 years; range, 49 to 83 years). This sample was drawn from a large multicenter trial on VaD and was expected to have a high prevalence of thalamic lesions. In a side-by-side review, including T1-weighted images as well, lesions were classified according to presumed underlying pathology.

Results—

The total number of thalamic lesions was 214. Two hundred eight (97%) were detected on T2-WI, but only 117 (55%) were detected on FLAIR (χ
2
=5.1;
P
<0.05). Although the mean size of lesions detected on T2-WI and not on FLAIR (4.4 mm) was significantly lower than the mean size of lesions detected on both sequences (6.7 mm) (
P
<0.001), 5 of the 29 lesions >10 mm on T2-WI were not visible on FLAIR. FLAIR detected only 81 (51%) of the 158 probable ischemic lesions and 30 (60%) of the 50 probable microbleeds.

Conclusions—

FLAIR should not be used as the only T2-weighted sequence to detect thalamic lesions in patients suspected of having VaD.
Blood Pressure Decrease During the Acute Phase of Ischemic Stroke Is Associated With Brain Injury and Poor Stroke Outcome
Authors: Castillo José , Leira Rogelio , García María M. , Serena Joaquín , Blanco Miguel , Dávalos Antoni
Published: January 2004

Background and Purpose—

Studies on the relation between blood pressure (BP) and stroke outcome have shown contradictory results. We explored the association of systolic (SBP) and diastolic (DBP) BP during acute stroke with early neurological deterioration, infarct volume, neurological outcome, and mortality at 3 months.

Methods—

We included 304 patients with acute ischemic stroke. SBP and DBP on admission and on the first day were the average values of all readings obtained in the emergency department and during a 24-hour period after patient allocation in the stroke unit.

Results—

A U-shaped effect was observed: for every 10 mm Hg ≤180 mm Hg of SBP, the risk of early neurological deterioration, poor outcome, and mortality increased by 6%, 25%, and 7%, respectively, whereas for every 10 mm Hg >180 mm Hg, the risk of early neurological deterioration increased by 40% and the risk of poor outcome increased by 23%, with no effect on mortality. Mean infarct volume increased 7.3 and 5.5 cm
3
for every 10 mm Hg ≤180 and >180 mm Hg. A similar pattern was found in patients with DBP ≤100 or >100 mm Hg. These effects disappeared after adjustment for the use of antihypertensive drugs and BP drop >20 mm Hg within the first day, with the latter being the more important prognostic factor of poor outcome.

Conclusions—

High and low SBP and DBP, as well as a relevant drop in BP, are associated with poor prognosis in patients with ischemic stroke.
Mild Postischemic Hypothermia Prolongs the Time Window for Gene Therapy by Inhibiting Cytochrome
c
Release
Authors: Zhao Heng , Yenari Midori A. , Sapolsky Robert M. , Steinberg Gary K.
Published: January 2004

Background and Purpose—

We showed previously that Bcl-2 overexpression with the use of herpes simplex viral (HSV) vectors improved striatal neuron survival when delivered 1.5 hours after stroke but not when delivered 5 hours after stroke onset. Here we determine whether hypothermia prolongs the therapeutic window for gene therapy.

Methods—

Rats were subjected to focal ischemia for 1 hour. Hypothermia (33°C) was induced 2 hours after insult and maintained for 3 hours. Five hours after ischemia onset, HSV vectors expressing Bcl-2 plus β-gal or β-gal alone were injected into each striatum. Rats were killed 2 days later.

Results—

Striatal neuron survival of Bcl-2–treated, hypothermic animals was improved 2- to 3-fold over control-treated, hypothermic animals and Bcl-2–treated, normothermic animals. Neuron survival among normothermic, Bcl-2–treated animals was not different from control normothermics or control hypothermics. Double immunostaining of cytochrome
c
and β-gal demonstrated that Bcl-2 plus hypothermia significantly reduced cytochrome
c
release.

Conclusions—

Postischemic mild hypothermia extended the time window for gene therapy neuroprotection using Bcl-2 and reduced cytochrome
c
release.
Wall Shear Stress Is Associated With Intima-Media Thickness and Carotid Atherosclerosis in Subjects at Low Coronary Heart Disease Risk
Authors: Irace Concetta , Cortese Claudio , Fiaschi Elio , Carallo Claudio , Farinaro Eduardo , Gnasso Agostino
Published: January 2004

Background and Purpose—

Systemic and local coronary heart disease (CHD) risk factors participate in atherogenesis. The role of wall shear stress, a major local risk factor, remains to be elucidated.

Methods—

Two hundred thirty-four subjects were carefully characterized for the presence of hypertension, hyperlipidemia, diabetes mellitus, obesity, and cigarette smoking and were divided into low- and high-risk groups. They underwent echo-Doppler examination of the carotid arteries. Atherosclerotic plaques and stenoses were detected, intima-media thickness (IMT) was measured, and wall shear stress was calculated.

Results—

One hundred eight subjects were classified as low-risk individuals. The prevalence of carotid atherosclerosis in this group was 18.5%. Wall shear stress was 24.23±7.21 dyne/cm
2
in individuals without atherosclerosis and 16.89±5.48 in those with atherosclerosis (
P
<0.000). In multiple regression analyses, wall shear stress, body mass index, and HDL cholesterol were inversely associated and total cholesterol was directly associated with the presence of atherosclerosis; only wall shear stress was associated with IMT. In the high-risk group the prevalence of atherosclerosis was 45.2%. Wall shear stress was 20.44±6.82 dyne/cm
2
in subjects without atherosclerosis and 17.84±6.88 dyne/cm
2
in those with atherosclerosis (
P
=0.037). Age was the only variable associated with both carotid atherosclerosis and IMT.

Conclusions—

In subjects traditionally considered at low CHD risk, intima-media thickening and carotid atherosclerosis are significantly associated with low wall shear stress. In contrast, in subjects at high CHD risk, the contribution of wall shear stress seems to be masked, and age becomes the only factor significantly associated with both carotid atherosclerosis and IMT.
Long-Term Outcome of Acute Spinal Cord Ischemia Syndrome
Authors: Nedeltchev Krassen , Loher Thomas J. , Stepper Frank , Arnold Marcel , Schroth Gerhard , Mattle Heinrich P. , Sturzenegger Matthias
Published: January 2004

Background and Purpose—

Current knowledge of long-term outcome in patients with acute spinal cord ischemia syndrome (ASCIS) is based on few studies with small sample sizes and <2 years’ follow-up. Therefore, we analyzed clinical features and outcome of all types of ASCIS to define predictors of recovery.

Methods—

From January 1990 through October 2002, 57 patients with ASCIS were admitted to our center. Follow-up data were available for 54. Neurological syndrome and initial degree of impairment were defined according to American Spinal Injury Association (ASIA)/International Medical Society of Paraplegia criteria. Functional outcome was assessed by walking ability and bladder control.

Results—

Mean age was 59.4 years; 29 were women; and mean follow-up was 4.5 years. The origin was atherosclerosis in 33.3%, aortic pathology in 15.8%, degenerative spine disease in 15.8%, cardiac embolism in 3.5%, systemic hypotension in 1.8%, epidural anesthesia in 1.8%, and cryptogenic in 28%. The initial motor deficit was severe in 30% (ASIA grades A and B), moderate in 28% (ASIA C), and mild in 42% (ASIA D). At follow-up, 41% had regained full walking ability, 30% were able to walk with aids, 20% were wheelchair bound, and 9% had died. Severe initial impairment (ASIA A and B) and female sex were independent predictors of unfavorable outcome (
P
=0.012 and
P
=0.043).

Conclusions—

Considering a broad spectrum of clinical presentations and origins, the outcome in our study was more favorable than in previous studies reporting on ASCIS subgroups with more severe initial deficits.
Synergistic Effect of Apolipoprotein E Polymorphisms and Cigarette Smoking on Risk of Ischemic Stroke in Young Adults
Authors: Pezzini Alessandro , Grassi Mario , Del Zotto Elisabetta , Bazzoli Elena , Archetti Silvana , Assanelli Deodato , Akkawi Nabil Maalikjy , Albertini Alberto , Padovani Alessandro
Published: January 2004

Background and Purpose—

The effect of apolipoprotein E (
APOE
) polymorphisms on stroke risk may be influenced by the coexistence of modifiable predisposing conditions. We explored the interactions of
APOE
genotypes and conventional risk factors in a case-control study of young adults with cerebral infarct.

Methods—

We analyzed 124 consecutive patients (age, 34.7±7.3 years) and 147 age- and sex-matched controls.
APOE
genotypes were determined by restriction fragment-length polymorphism analysis.

Results—

The prevalence of the ε4 allele and ε34 genotype was slightly higher in cases than in controls (0.125 versus 0.071 and 0.242 versus 0.136, respectively). Carriers of the ε34 genotype and ε4 allele were associated with an increased risk of stroke on multivariate analysis compared with the ε33 genotype and non-ε4 carriers, respectively (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.10 to 4.76; and OR, 2.27; 95% CI, 1.13 to 4.56). ORs for stroke were 2.99 (95% CI, 1.64 to 5.45), 2.69 (95% CI, 1.25 to 5.77), and 5.39 (95% CI, 1.59 to 18.30) for smokers with the ε33 genotype, nonsmokers with the ε34 genotype, and smokers with the ε34 genotype, respectively, compared with nonsmokers with the ε33 genotype. Similar results were obtained when ε4 carriers and non-ε4 carriers were compared in the same interaction model. No significant interaction between
APOE
and hypertension was found.

Conclusions—

In young adults, the
APOE
ε4 allele and cigarette smoking act synergistically, increasing an individual’s propensity to have a cerebral ischemic event. This finding may help in determining an individual’s predisposition to stroke and more targeted preventive interventions.
Ischemic Stunning of the Brain
Authors: Alexandrov Andrei V. , Hall Christiana E. , Labiche Lise A. , Wojner Anne W. , Grotta James C.
Published: January 2004

Background and Purpose—

Early arterial recanalization (ER) with intravenous tissue plasminogen activator (tPA) can lead to dramatic clinical recovery, whereas some patients do not experience immediate clinical improvement.

Methods—

Consecutive patients received tPA 0.9 mg/kg IV within 3 hours after symptom onset. All had M1 or M2 middle cerebral artery occlusions on pretreatment transcranial Doppler. Patients were continuously monitored for 2 hours after bolus. ER was defined as the Thrombolysis in Brain Ischemia intracranial flow increase by ≥1 grade. Stroke severity (National Institutes of Health Stroke Scale [NIHSS]) and recovery (modified Rankin Scale) were assessed independently of transcranial Doppler.

Results—

One hundred twenty patients (mean age, 68±15 years; 63 women; median NIHSS, 17; range, 5 to 29; 90% with ≥10 points) received tPA at a median of 120 minutes, 50% within the first 2 hours. ER was observed in 73 patients (32 complete, 41 partial). No immediate clinical changes (n=23) or worsening (by 1 to 6 points on NIHSS, n=4) was observed in 37% of ERs (nonresponders). Complete ER was found in 8 of these 27 patients. At 24 hours, 22 of 27 patients (82%) had persisting deficits of NIHSS ≥10 points, yet 37% of these nonresponders (10 of 27) still achieved good outcome (modified Rankin score, 0 to 2) at 3 months. Among nonresponders with good outcome, 100% had detectable residual flow signals, and 70% had compensatory flow diversion on prebolus transcranial Doppler compared with 65% and 29% of nonresponders with poor outcome (
P
<0.05). Compared with responders (n=46), nonresponders had similar prebolus median NIHSS of 16 to 17 points, bolus times of 120 to 132 minutes, median speed of thrombolysis (30 minutes), and ER times of 190 to 193 minutes after onset. Reocclusion occurred in 3 of 4 patients with clinical worsening, 30% of other nonresponders, and 22% of responders. Symptomatic hemorrhage rate was 4% in both groups. At 3 months, mortality was 33% in nonresponders compared with 9% in responders (
P
=0.001).

Conclusions—

After successful arterial ER with tPA therapy, lack of early clinical changes or worsening is relatively common (37%) and appears to be independent of time to tPA bolus or reperfusion. However, with tPA alone, at least one third of these nonresponders still achieved good outcomes at 3 months, suggesting the possibility of a “stunned brain” syndrome with delayed recovery. Several different mechanisms may potentially account for this phenomenon.
Prospective Evaluation of the Alcohol Dehydrogenase γ1/γ2 Gene Polymorphism and Risk of Stroke
Authors: Zee Robert Y.L. , Ridker Paul M. , Cook Nancy R.
Published: January 2004

Background and Purpose—

Genetic polymorphism of the alcohol dehydrogenase type 3 gene (
ADH1C
) has recently been associated with reduced risk of myocardial infarction. However, data on risk of stroke are not available.

Methods—

We examined the possible association between the
ADH1C
γ1/γ2 polymorphism and risk of stroke in a prospective, nested case-control sample from the Physicians’ Health Study of 14 916 apparently healthy men who were followed over a 12-year period. A total of 320 incident stroke cases and 550 age- and smoking-matched controls were genotyped.

Results—

All observed genotype frequencies were in Hardy-Weinberg equilibrium. The allele and genotype distributions of the polymorphism tested were similar between cases and controls, such that the relative risk of stroke was 1.04 for
ADH1C
γ1/γ2 (95% CI=0.85 to 1.28;
P
=0.65) assuming an additive mode of inheritance. Contrary to prior findings for myocardial infarction, no evidence of association was observed to suggest an effect modification of
ADH1C
genotypes with the level of alcohol consumption on the risk of stroke. Similar findings were observed in subgroup analysis restricted to ischemic events.

Conclusions—

In this large, prospective study, we found little evidence that the
ADH1C
γ1/γ2 polymorphism is associated with risk of future stroke. These data raise the possibility of important pathologic differences in ischemia between the coronary and cerebral circulations.
Simulating Market Dynamics: Interactions between Consumer Psychology and Social Networks
Authors: Janssen Marco A. , Jager Wander
Published: January 2004

Markets can show different types of dynamics, from quiet markets dominated by one or a few products, to markets with continual penetration of new and reintroduced products. In a previous article we explored the dynamics of markets from a psychological perspective using a multi-agent simulation model. The main results indicated that the behavioral rules dominating the artificial consumer's decision making determine the resulting market dynamics, such as fashions, lock-in, and unstable renewal. Results also show the importance of psychological variables like social networks, preferences, and the need for identity to explain the dynamics of markets. In this article we extend this work in two directions. First, we will focus on a more systematic investigation of the effects of different network structures. The previous article was based on Watts and Strogatz's approach, which describes the small-world and clustering characteristics in networks. More recent research demonstrated that many large networks display a scale-free power-law distribution for node connectivity. In terms of market dynamics this may imply that a small proportion of consumers may have an exceptional influence on the consumptive behavior of others (hubs, or early adapters). We show that market dynamics is a self-organized property depending on the interaction between the agents' decision-making process (heuristics), the product characteristics (degree of satisfaction of unit of consumption, visibility), and the structure of interactions between agents (size of network and hubs in a social network).
World-Size Global Markets Lead to Economic Instability
Authors: Louzoun Yoram , Solomon Sorin , Goldenberg Jacob , Mazursky David
Published: January 2004

Economic and cultural globalization is one of the most important processes humankind has been undergoing lately. This process is assumed to be leading the world into a wealthy society with a better life. However, the current trend of globalization is not unprecedented in human history, and has had some severe consequences in the past. By applying a quantitative analysis through a microscopic representation we show that globalization, besides being unfair (with respect to wealth distribution), is also unstable and potentially dangerous as one event may lead to a collapse of the system. It is proposed that the optimal solution in controlling the unwanted aspects and enhancing the advantageous ones lies in limiting competition to large subregions, rather than making it worldwide.
Iterated Learning: A Framework for the Emergence of Language
Authors: Smith Kenny , Kirby Simon , Brighton Henry
Published: January 2004

Language is culturally transmitted. Iterated learning, the process by which the output of one individual's learning becomes the input to other individuals' learning, provides a framework for investigating the cultural evolution of linguistic structure. We present two models, based upon the iterated learning framework, which show that the poverty of the stimulus available to language learners leads to the emergence of linguistic structure. Compositionality is language's adaptation to stimulus poverty.
Evolution of an Optimal Lexicon under Constraints from Embodiment
Authors: Zuidema Willem , Westermann Gert
Published: January 2004

Research in language evolution is concerned with the question of how complex linguistic structures can emerge from the interactions between many communicating individuals. Thus it complements psycholinguistics, which investigates the processes involved in individual adult language processing, and child language development studies, which investigate how children learn a given (fixed) language. We focus on the framework of language games and argue that they offer a fresh and formal perspective on many current debates in cognitive science, including those on the synchronic-versus-diachronic perspective on language, the embodiment and situatedness of language and cognition, and the self-organization of linguistic patterns. We present a measure for the quality of a lexicon in a population, and derive four characteristics of the optimal lexicon: specificity, coherence, distinctiveness, and regularity. We present a model of lexical dynamics that shows the spontaneous emergence of these characteristics in a distributed population of individuals that incorporate embodiment constraints. Finally, we discuss how research in cognitive science could contribute to improving existing language game models.
Emergent Patterns of Mate Choice in Human Populations
Authors: Simão Jorge , Todd Peter M.
Published: January 2004

We present a model of human mate choice that shows how realistic population-level patterns of assortative mating can self-organize and emerge from the behavior of individuals using simple mate search rules. In particular, we model plausible psychological mechanisms for mate search and choice in a realistic social ecology. Through individual interactions, patterns emerge that match those observed in typical human societies, particularly with regard to correlated quality levels within couples, distributions of the ages at which couples mate, and effects of skewed sex ratios on these mating age distributions.
Emergent Properties in Small-Scale Societies
Authors: Read Dwight W.
Published: January 2004

A multi-agent simulation is used to explore the relationship between the micro and the macro levels in small-scale societies. The simulation demonstrates, using an African hunter-gatherer group (the !Kung san) as a case study, the way in which population stability may arise from culturally framed, micro-level decision making by women about spacing of births. According to the simulation, population stability as an emergent property has different implications, depending on resource density. Data on Australian hunter-gatherer groups are presented that support the implications of the simulation. !Kung san micro-level cultural rules on incestuous marriages are shown to have macro-level consequences in the form of marriages between residential camps. Between-camp marriages have significant implications for access to resources and thereby for population dynamics of the group as a whole.
The Evolution of Social Behavior in the Prehistoric American Southwest
Authors: Gumerman George J. , Swedlund Alan C. , Dean Jeffrey S. , Epstein Joshua M.
Published: January 2004

Long House Valley, located in the Black Mesa area of northeastern Arizona (USA), was inhabited by the Kayenta Anasazi from circa 1800 B.C. to circa A.D. 1300. These people were prehistoric precursors of the modern Pueblo cultures of the Colorado Plateau. A rich paleoenvironmental record, based on alluvial geomorphology, palynology, and dendroclimatology, permits the accurate quantitative reconstruction of annual fluctuations in potential agricultural production (kg maize/hectare). The archaeological record of Anasazi farming groups from A.D. 200 to 1300 provides information on a millennium of sociocultural stasis, variability, change, and adaptation. We report on a multi-agent computational model of this society that closely reproduces the main features of its actual history, including population ebb and flow, changing spatial settlement patterns, and eventual rapid decline. The agents in the model are monoagriculturalists, who decide both where to situate their fields and where to locate their settlements.
VIRTUE AND TALENT: WOMEN AND FUSHI IN EARLY CHINA
Authors: Yiqun Zhou
Published: January 2004

A study of two early historical records shows that women had a share in fushi (presenting the Odes), a social ritual and high art that is otherwise known as a preserve of the male elite. The paper retrieves the context of women's participation and analyzes the Confucian morality underlying the portrayals of the two female practitioners, both in light of the principle of sexual separation. The formulation of the relationship between female virtue and talent in these early records exemplifies the parameters of the later development of the dichotomy, and the metamorphosis of the images of the two female fushi practitioners in the first-century-BCE Lienü zhuan represents the first definitive version of the orthodox Confucian position on that issue.
THE BOURGEOIS HOUSEWIFE AS LABORER IN LATE QING AND EARLY REPUBLICAN SHANGHAI
Authors: Orliski Constance
Published: January 2004

During the late Qing and early Republic, Chinese reformers, such as Liang Qichao, argued that because all women were "consumers" and not "producers," they had weakened the state by posing a financial burden to the family and a collective impediment to economic development. This article examines the diverse responses inspired by this construction of womanhood as they appeared in the burgeoning female press of the period. Deploying this new medium of communication, the women and men who endeavored to define nügong, female labor, embedded in their representations of "women's work" contrary interpretations of what it meant to be a productive citizen, an industrious member of the middle class, and an educated woman who labored in public or private. Thus, nügong discourse not only considered new characterizations of female labor in the context of a society and an economy in transition, but it also acted as a site for negotiating competing and intersecting conceptions of nationalism, class, and gender.
VISUAL EVIDENCE FOR THE EVOLUTION OF "POLITICALLY CORRECT" DRESS FOR WOMEN IN EARLY TWENTIETH CENTURY SHANGHAI
Authors: Laing Ellen Johnston
Published: January 2004

In China in the first half of the twentieth century, official and unofficial efforts were made to regulate or influence women's dress, despite the fact that for urban, sophisticated, independent, middle-class urbanites, fashions were largely determined by the women who wore them. The first official mandate for women's dress, promulgated by the new Republican government in 1912, had little lasting effect. Unofficial efforts in 1915 and 1920 to influence women's garb, stemming from the antiforeign National Goods Movement, which the textile industry had originated much earlier and which urged patriotic Chinese to "buy Chinese," was also largely inconsequential. Only the Nationalist official designation in 1927 of a "national" feminine dress was effective. Using dated visual evidence from the print media, this paper assesses the failures and successes of these two official and one unofficial attempt to define proper attire for Chinese women.
TEXTILES AND FEMALE VIRTUE IN EARLY IMPERIAL CHINESE HISTORICAL WRITING
Authors: Hinsch Bret
Published: January 2004

In China, cloth making became more than just an economic activity. The female cloth maker was an important cultural image in early imperial China. Writers of various persuasions agreed that making cloth is a highly virtuous female activity, although they disagreed as to why this particular kind of labor is good. The moralization of cloth making became an important component of early Chinese female identity. Influential male writers and women of different social strata deployed this image for powerful rhetorical effect.
Sextus Empiricus and the Tripartition of Time
Authors: Warren James
Published: January 2004

A discussion of the arguments against the existence of time based upon its tripartition into past, present, and future found in SE M 10.197-202. It uncovers Sextus' major premises and assumptions for these arguments and, in particular, criticises his argument that the past and future do not exist because the former is no longer and the latter is not yet. It also places these arguments within the larger structure of Sextus' arguments on time in SE M 10 and considers these arguments as an example of his general strategy for producing ataraxia by assembling opposing sets of argument on a given question.
Formation of Hollow Spheres of Hydroxyapatite in Plasma Spraying
Authors: Sun R. X. , Lu Y. P. , Li M. S.
Published: January 2004

Hydroxyapatite (HA) particles are subjected to melting at high temperature when used to plasma spray a coating onto a metallic substrate. Accordingly, changes in the melting temperature and morphology of the HA particles are of importance in defining the coating characteristics. The HA particles were plasma sprayed into water and their melting temperature and structure change were analysed using SEM. The results showed that, under the same conditions of spraying, the melting level changed with particle size and more hollow spheres were formed by the molten HA particles, which may have resulted from gaseous P2O5 and H2O arising from decomposed Ca10(PO4)6(OH)2 at a high temperature and also from the volume contraction of HA powder particles as a result of fast cooling. In this study, only the morphology of the HA hollow spheres was examined. These hollow spheres will have important applications in the tissue engineering field and in the optimisation of plasma spraying parameters for HA coatings.
Low Temperature Plasma Nitriding Characteristics of Precipitation Hardening Stainless Steel
Authors: Sun Y. , Bell T.
Published: January 2004

The low temperature plasma nitriding behaviour of 17-4PH type precipitation hardening stainless steel was investigated in the present work. The morphology, thickness, hardness and X-ray diffraction characteristics of the nitrided layers produced at temperatures between 350 ° C and 450 ° C were studied. It was found that, at temperatures lower than 425 ° C, a thin, hard nitrided layer exhibiting a ‘white’ and featureless morphology could be produced on the steel investigated. X-ray diffraction analysis revealed that this layer was X-ray amorphous, as derived from its lack of Bragg reflection peaks in the diffraction pattern. At higher nitriding temperatures, chromium and iron nitrides began to form in the nitrided layer, leading to a transition in nitriding kinetics and a decrease in hardness. The possible mechanisms relating to the formation of the amorphous-like nitrided layer at sufficiently low temperatures are discussed in terms of the theory of solid state diffusion reaction for amorphous alloy formation.
New Method for Preparing Cubic Boron Nitride Hardened Layers
Authors: Wang J. , Liu X. , Wang X. , Chen Y.
Published: January 2004

Hardened layers 0.15 - 0.2 mm thick were prepared by a duplex treatment combining boronising at a temperature of 900 ° C for 5 h and plasma immersion ion implantation with nitrogen ions at an implanting energy of 60 keV to a dose of 3×1017 atoms cm -2. at a temperature of 400°C on 50Mn steel (0.5C - 0.8Mn, wt-%) substrates. Cubic boron nitride, hexagonal boron nitride, B2O3, FeB, Fe2B were found in the hardened layers by X-ray photoelectron spectroscopy and X-ray diffraction. The amount of c-BN phase dominates in the region from the surface of the hardened layers to a depth of 60 nm. The friction properties and hardness of the hardened layers were determined by standard sphere on disc sliding friction experiments at room temperature under unlubricated conditions and by Vickers microhardness experiments under different loads on duplex treated specimens and on the specimens treated alone by boronising. The results of the experiments showed that the duplex specimens of 50Mn steel had a far greater (up to 44 HV(0.1 N)) hardness and wear resistance than the specimens of 50Mn steel treated only by boronising.