bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal low-protein diet in rat pregnancy programs blood pressure through sex-specific mechanisms
Authors: McMullen Sarah , Langley-Evans Simon C.
Published: September 2004

Animal models support human epidemiological studies in demonstrating a relationship between impaired fetal growth and risk of adult hypertension. Undernutrition during pregnancy exerts programming effects on the developing kidney, and modulation of angiotensin receptor (ATR) expression has been observed persisting into adult life. Fetal overexposure to glucocorticoids is thought to be central to the nutritional programming of blood pressure and may act through an interaction with ATR expression. Pregnant female Wistar rats were fed a control ( n = 6) or a maternal low-protein diet (MLP; n = 17) throughout pregnancy. The glucocorticoid dependency of MLP effects was tested using metyrapone, an inhibitor of corticosterone synthesis. MLP-fed rats were injected twice daily with metyrapone, metyrapone plus corticosterone, or vehicle over days 1–14 of pregnancy. At delivery, all animals were fed standard laboratory chow. MLP-exposed offspring 4 wk of age exhibited increased systolic blood pressure compared with controls ( P < 0.05), which proved to be glucocorticoid dependent in males only. AT1R mRNA expression was independent of in utero dietary treatment. AT2R mRNA expression was downregulated in MLP-exposed females only ( P < 0.05) and in a glucocorticoid-independent manner. Male offspring exhibited glucocorticoid-dependent hypertension with no modulation of renal ATR mRNA expression. In contrast, female offspring exhibited glucocorticoid-independent hypertension associated with reduced expression of renal AT2R mRNA. These data do not support the hypothesis that an interaction between glucocorticoid and ATR mRNA expression underlies the nutritional programming of blood pressure but instead suggest two independent mechanisms acting in a sex-specific manner.
Nitrite-derived nitric oxide formation following ischemia-reperfusion injury in kidney
Authors: Okamoto Masumi , Tsuchiya Koichiro , Kanematsu Yasuhisa , Izawa Yuki , Yoshizumi Masanori , Kagawa Susumu , Tamaki Toshiaki
Published: September 2004

Nitric oxide (NO) is synthesized from l-arginine by nitric oxide synthase (NOS), and nitrite and nitrate are believed to be waste forms of NO. We previously reported an enzyme-independent pathway of NO generation from nitrite in acidic conditions. In this study, we show nitrite-derived NO formation in renal ischemia-reperfusion injury using electron paramagnetic resonance (EPR) spectroscopy. In this experiment, we utilized a stable isotope of [15N]nitrite as a source of nitrite to distinguish l-arginine-derived NO from [15N]nitrite-derived 15NO. Intravenous infusion of a stable isotope of [15N]nitrite (15NO2−) facilitated the formation of Hb15NO during renal ischemia, which demonstrated that the origin of NO was nitrite. The EPR signal of Hb15NO in kidney appeared after 40 min of renal ischemia, and renal reperfusion decreased the Hb15NO level in the kidney and increased it in blood by contrast. In addition, the amount of HbNO was nitrite concentration dependent, and this formation was NOS independent. Our findings suggest that nitrite can be an alternative source of NO in ischemic kidney and that it binds with hemoglobin and then is spread by the circulation after reperfusion.
Effect of Cerebrospinal Fluid Leakage on Wound Healing in Flap Surgery: Histological Evaluation
Authors: Babuccu Orhan , Kalaycı Murat , Peksoy Irfan , Kargı Eksal , Cagavi Ferda , Numanoğlu Gamze
Published: September 2004

The aim of this study was to find out the effect of CSF leakage on wound healing after flap surgery. Sixteen male Wistar rats were used. The superiorly based rectangular dorsal skin flap 3 × 3 cm was elevated at the interscapular region. Through this opening, paraspinal muscle dissection and three-level bilateral laminectomy were done. Finally, a dura defect with a diameter of 3–4 mm was created. In the control group, laminectomy was performed as in the study group but the dura was left intact. Persistent CSF leakage was confirmed using isotope cisternography. At the end of 2-week study period, there was no necrosis, infection, or dehiscence of the flap in either group. On necroscopy, cyst formation over the dura defect was detected in 4 animals of the study group. Another gross finding in this group was intensive vascularization of the undersurface of the flap and wound bed. With HE staining, the tissue sections from the study group revealed new vessel formation with small diameter, increase in the reactional mesenchymal tissue, granulation tissue, degeneration of the striated muscle fibers, dystrophic calcifications, fat necrosis, and coagulation necrosis (ischemic necrosis). In the control group, there was only minimal lymphocytic invasion of the subdermal plane. In this study, we have shown that CSF leakage itself has effects on wound healing in the absence of known causative factors.
A Giant Intramedullary Spinal Epidermoid Cyst of the Cervicothoracic Region
Authors: Çataltepe Oğuz , Berker Mustafa , Akalan Nejat
Published: September 2004

Intramedullary epidermoid cysts of the spinal cord are rare lesions. The authors report a case of giant intramedullary epidermoid cyst at the cervicothoracic region. A 6-year-old boy presented with motor and sensory loss related to a spinal intramedullary epidermoid cyst. Almost all cyst content was liquid and it was surgically removed totally in two successive operations. To the author’s knowledge, this is the largest intramedullary epidermoid cyst published in the literature and no other case of intramedullary epidermoid cyst with a complete liquid content has been reported before. The authors discuss the clinical features, MR imaging characteristics and surgical findings of this rare tumor and review the associated literature.
GABA Transporters GAT-1 and GAT-3 in the Human Dorsolateral Prefrontal Cortex in Schizophrenia
Authors: Schleimer Sonja B. , Hinton Tina , Dixon Gavin , Johnston Graham A.R.
Published: September 2004

This study aimed to investigate the binding affinity of [3H]GABA and [3H]β-alanine to GABA transporters GAT-1 and GAT-3 in the human dorsolateral prefrontal cortex (Brodmanns’ area 9) in schizophrenia. Using post mortem tissue from individuals diagnosed with schizophrenia (n = 6) and control subjects (n = 6), the density of GAT-1 was established by displacing [3H]GABA with muscimol, and for GAT-3 [3H]β-alanine was used. Data analysis showed a significant decrease of GAT-1 levels (45%), and a significant increase of GAT-3 density (23%) within the dorsolateral prefrontal cortex of individuals diagnosed with schizophrenia when compared to age- and sex-matched controls. The observed decrease of GAT-1 could be explained as a consequence of the GABA hypo-function or the result of volumetric shrinkage of the cerebral cortex previously reported in this disease. The observed elevation of GAT-3 levels could be due to a compensatory effect for any functional loss of GABA re-uptake by the decreased GAT-1 levels.
Platelet 5-HT Uptake in Boys with Conduct Disorder
Authors: Stadler C. , Schmeck K. , Nowraty I. , Müller W.E. , Poustka F.
Published: September 2004

Dysregulation of serotonergic function has been found to be associated with aggression in animals, human adults and adolescents. However, studies with children have shown conflicting results. The objective of this study was to investigate whether the kinetic characteristics (Vmax and Km) of 5-HT uptake in platelets are different in children with the diagnosis of conduct disorder according to ICD-10 and healthy age-matched controls. In addition to the standardized assessment of general psychopathology, methods assessing narrowband aggressive symptoms (Child Behavior Checklist) and emotional reactivity to an experimentally induced provocation (Taylor’s competitive reaction time task) were used in both groups. We found a trend for a lower mean Vmax of platelet 5-HT uptake in 14 conduct-disordered boys compared with healthy controls (n = 15). If, however, 2 patients with a low degree of aggression and emotional reactivity were excluded, the difference became significant (mean = 4.27, SD = 3.49 in patients and mean = 8.45, SD = 4.63 in controls). A significant negative correlation was found between parent-rated aggression scores and Vmax (r = –0.41, p < 0.05, n = 29). These data suggest that dysfunction of 5-HT transport mechanisms might be associated with specific behavioral symptoms in conduct-disordered children.
Efficacy of Erythropoietin on Dialysis in Patients with Beta Thalassemia Minor
Authors: Di Iorio Biagio , de Nicola Luca , Bellizzi Vincenzo , Minutolo Roberto , Zamboli Pasquale , Rubino Roberto , Fuiano Giorgio , Conte Giuseppe
Published: September 2004

Background: It is unknown whether chronic erythropoietin (EPO) treatment is able to normalize hemoglobin (Hb) levels and ameliorate cardiac remodeling avoiding blood transfusions in uremic blood transfusion-dependent patients with β-thalassemia minor (β-thal). Methods: In 12 hemodialysis (HD) patients with β-thal, requiring blood transfusions despite EPO therapy, we planned to increase Hb levels up to the target levels (11–12 g/dl) within a one-year period by administering progressively higher doses of EPO (correction phase). We also planned to maintain the Hb target for an additional year (maintenance phase). Results: In the year before the study, patients required 3.3 ± 0.9 units of packed red blood cells. At baseline, the Hb level obtained with an EPO dose of 212 ± 73 U/kg/week i.v. was 8.2 ± 0.8 g/dl. The EPO dose was gradually increased within the first year up to 458 ± 78 U/kg/week at month 12 (correction phase) and then significantly tapered down during the maintenance phase (390 ± 54 U/kg/week at month 24). During the correction phase, the Hb levels markedly increased (11.1 ± 0.3 g/dl at month 12) and did not change in the maintenance phase. No blood transfusion was required throughout the 2 years of follow-up. Left ventricular (LV) mass index progressively decreased from the basal value of 144 ± 12 to 124 ± 11 g/m2 in the first year and normalized in all patients at month 24 (109 ± 12 g/m2, p < 0.001); this occurred in the absence of any change of LV cavity volume index (<90 ml/m2). Conclusions: In HD transfusion-dependent patients with β-thal, the administration of high EPO dose for 2 years permits the attainment and the maintenance of Hb targets without blood transfusions. This therapeutic approach permits a complete remission of concentric LV hypertrophy without any adverse effects on the vascular system.
Increased Expression of the DNA-Binding Cytokine HMGB1 in Human Atherosclerotic Lesions
Authors: Kalinina N. , Agrotis A. , Antropova Y. , DiVitto G. , Kanellakis P. , Kostolias G. , Ilyinskaya O. , Tararak E. , Bobik A.
Published: September 2004

Objective—Atherosclerosis is a chronic inflammatory response of the arterial wall to injury. High-mobility group box 1 (HMGB1) is a DNA-binding protein, which on release from cells exhibits potent inflammatory actions. We examined its expression in atherosclerotic lesions and regulation by cytokines.

Methods and Results—In atherosclerotic lesions, HMGB1 protein is expressed by endothelial cells, some intimal smooth muscle cells, and macrophages. As atherosclerosis develops and progresses from fatty streaks to fibrofatty lesion, the number of HMGB1-producing macrophages increases markedly. Studies using the THP-1 cell line indicated that HMGB1 mRNA expression could be markedly upregulated by inflammatory cytokines, interferon (IFN)-γ, tumor necrosis factor (TNF)-α and also transforming growth factor (TGF)-β. IFN-γ, TNF-α, TWEAK, and TGF-β induced an intracellular redistribution of HMGB1 and stimulated secretion by THP-1 cells and human blood monocytes. Inhibitors of MEK1/MEK2, protein kinase C, and PI-3/Akt, which inhibit lysosomal degranulation and mRNA translation, attenuated cytokine-induced HMGB1 secretion.

Conclusions—Macrophage is the major cell type responsible for HMGB1 production in human atherosclerotic lesions. Inflammatory cytokines and TGF-β increase HMGB1 expression and secretion by monocyte/macrophages. HMGB1 appears to be a common mediator of inflammation induced by inflammatory cytokines and is likely to contribute to lesion progression and chronic inflammation.
Shear Stress Insensitivity of Endothelial Nitric Oxide Synthase Expression as a Genetic Risk Factor for Coronary Heart Disease
Authors: Cattaruzza Marco , Guzik Tomasz J. , Słodowski Wojciech , Pelvan Ayşegül , Becker Jürgen , Halle Martin , Buchwald Arnd B. , Channon Keith M. , Hecker Markus
Published: September 2004

Coronary heart disease (CHD) is based on the development of atherosclerosis in coronary arteries. Shear stress-induced endothelial nitric oxide (NO) release not only contributes to local blood pressure control but also effectively helps to retard atherosclerosis. Therefore, functionally relevant polymorphisms in the endothelial NO synthase (NOS-3) gene may contribute to the development of CHD. NOS-3 expression was analyzed in endothelial cells isolated from umbilical cords genotyped for the
−786
C/T single nucleotide polymorphism (SNP) of the human
nos-3
gene. Moreover, NO-dependent relaxation was examined in segments of saphenous vein isolated from genotyped patients undergoing aortocoronary bypass surgery, and patients subjected to quantitative coronary angiography were genotyped to verify an association between this SNP and CHD. Shear stress-induced NOS-3 mRNA and protein expression was present in TT and CT genotype cells but absent in cells with CC genotype. Pretreatment of these cells with a decoy oligonucleotide comprising position −800 to −779 of the C-type
nos-3
promoter reconstituted shear stress-induced NOS-3 expression. These results were confirmed by reporter gene analysis with the corresponding
nos-3
promoter luciferase constructs. In addition, the NO-mediated relaxant response of vein grafts from CC genotype patients was significantly attenuated as compared with the CT or TT genotype, and in CHD-positive patients, the CC genotype was significantly more frequent (19.0%) than in CHD-negative patients (4.4%). The
−786
C/T SNP of the
nos-3
gene thus constitutes a genetic risk factor for CHD, presumably due to binding of an inhibitory transcription factor to the C-type promoter blocking shear stress-dependent maintenance of NOS-3 expression.
Dichloroacetate Prevents and Reverses Pulmonary Hypertension by Inducing Pulmonary Artery Smooth Muscle Cell Apoptosis
Authors: McMurtry M. Sean , Bonnet Sebastien , Wu Xichen , Dyck Jason R.B. , Haromy Alois , Hashimoto Kyoko , Michelakis Evangelos D.
Published: September 2004

The pulmonary arteries (PA) in pulmonary arterial hypertension (PAH) are constricted and remodeled;. They have suppressed apoptosis, partly attributable to suppression of the bone morphogenetic protein axis and selective downregulation of PA smooth muscle cell (PASMC) voltage-gated K
+
channels, including Kv1.5. The Kv downregulation-induced increase in [K
+
]
i
, tonically inhibits caspases, further suppressing apoptosis. Mitochondria control apoptosis and produce activated oxygen species like H
2
O
2
, which regulate vascular tone by activating K
+
channels, but their role in PAH is unknown. We show that dichloroacetate (DCA), a metabolic modulator that increases mitochondrial oxidative phosphorylation, prevents and reverses established monocrotaline-induced PAH (MCT-PAH), significantly improving mortality. Compared with MCT-PAH, DCA-treated rats (80 mg/kg per day in drinking water on day 14 after MCT, studied on day 21) have decreased pulmonary, but not systemic, vascular resistance (63% decrease,
P
<0.002), PA medial thickness (28% decrease,
P
<0.0001), and right ventricular hypertrophy (34% decrease,
P
<0.001). DCA is similarly effective when given at day 1 or day 21 after MCT (studied day 28) but has no effect on normal rats. DCA depolarizes MCT-PAH PASMC mitochondria and causes release of H
2
O
2
and cytochrome c, inducing a 10-fold increase in apoptosis within the PA media (TUNEL and caspase 3 activity) and decreasing proliferation (proliferating-cell nuclear antigen and BrdU assays). Immunoblots, immunohistochemistry, laser-captured microdissection-quantitative reverse-transcription polymerase chain reaction and patch-clamping show that DCA reverses the Kv1.5 downregulation in resistance PAs. In summary, DCA reverses PA remodeling by increasing the mitochondria-dependent apoptosis/proliferation ratio and upregulating Kv1.5 in the media. We identify mitochondria-dependent apoptosis as a potential target for therapy and DCA as an effective and selective treatment for PAH.
Motor Cortex Excitability After Cerebellar Infarction
Authors: Liepert J. , Kucinski T. , Tüscher O. , Pawlas F. , Bäumer T. , Weiller C.
Published: September 2004

Background and Purpose—

The cerebellum has an influence on motor excitability. We investigated if the location of a cerebellar infarction was crucial for changes of motor cortex excitability and if the electrophysiological findings were correlated with motor performance.

Methods—

Transcranial magnetic stimulation was applied to study intracortical inhibition (ICI), intracortical facilitation (ICF), motor thresholds, and corticospinal excitability. Dexterity as a measure of motor performance was tested with the Nine-Hole-Peg Test (9HPT). Ratios (affected/unaffected) were also calculated.

Results—

ICI and ICF ratios were negatively correlated with 9HPT ratios in all patients (n=9). Compared with an age-matched control group, patients with lesions in the territory of the superior cerebellar artery (SCA) (n=3) or a lesion rostral of the dentate nucleus (n=1) had abnormally enhanced ICI and a loss of ICF (3 patients). Dexterity was impaired in all 4 patients. Motor excitability and motor performance normalized over the subsequent weeks. Patients with an infarct either in the territory of the anterior inferior cerebellar artery (n=2) or in the territory of the posterior inferior cerebellar artery (n=3) displayed motor excitability and motor performance within the normal range.

Conclusion—

The superior part of the cerebellum has a strong influence on motor cortex excitability. We suggest that the enhancement of motor inhibition and reduction of motor facilitation is mediated by an impairment of the deep cerebellar nuclei.
Risk Factors for Vascular Dementia and Alzheimer Disease
Authors: Gorelick Philip B.
Published: September 2004

Alzheimer disease and vascular cognitive impairment are important causes of cognitive decline in the elderly. It has now been shown that vascular risk factors have measurable negative effects on the brain and are associated with cognitive impairment. We review vascular factors that might be responsible to cognitive decline in Alzheimer disease and vascular cognitive impairment and the corresponding intervenvations that might prevent cognitive impairment as we age.
Constraint-Induced Movement Therapy
Authors: Grotta James C. , Noser Elizabeth A. , Ro Tony , Boake Corwin , Levin Harvey , Aronowski Jarek , Schallert Timothy
Published: September 2004

Constraint-induced movement therapy improves outcome after chronic stroke, conforms experimental observations of neuronal plasticity, and proves the efficacy of intensive occupational therapy. More acutely instituted constraint-induced movement therapy has both practical and theoretic risks and benefits that deserve further careful evaluation.
Ultrasound Identification and Lysis of Clots
Authors: Alexandrov Andrei V.
Published: September 2004

Poor recovery after systemic tissue plasminogen activator (tPA) therapy could result from the initial severity of ischemic insult and slow and incomplete thrombolysis. Persisting arterial occlusions can be identified at bedside using portable diagnostic ultrasound by detecting residual flow signals around the thrombus (thrombolysis in brain ischemia [TIBI] flow grades). A narrow pulsed ultrasound beam can be steadily aimed at the thrombus/residual flow interface, exposing more thrombus surface and structures to tPA, and tPA activity can be enhanced with 2 MHz transcranial Doppler (TCD). A randomized, multicenter, clinical trial called CLOTBUST (Combined Lysis of Thrombus in Brain ischemia using transcranial Ultrasound and Systemic tPA) trial showed a 49% rate of complete recanalization or dramatic clinical recovery from stroke within 2 hours after tPA bolus when tPA infusion was continuously monitored with TCD, compared with 30% among patients who received tPA without ultrasound monitoring (
P
=0.03, number needed to treat, 5). Early complete recanalization was sustained at 2 hours by 38% of monitored patients compared with 12.7% controls. The CLOTBUST Trial showed a trend toward sustaining complete recovery at 3 months (41.5% versus 28%, modified Rankin Scale scores 0 to 1), subject for a pivotal phase III trial. Ultrasound is an inexpensive, noninvasive, real-time monitoring tool to identify nonresponders to systemic tPA and select patients with persisting occlusions for intraarterial interventions. Early brain perfusion augmentation, complete recanalization, and dramatic clinical recovery are feasible goals for ultrasound-enhanced thrombolysis.
Glutamate Receptor Blockade Attenuates Glucose Hypermetabolism in Perihematomal Brain After Experimental Intracerebral Hemorrhage in Rat
Authors: Ardizzone Timothy D. , Lu Aigang , Wagner Kenneth R. , Tang Yang , Ran Ruiqiong , Sharp Frank R.
Published: September 2004

Background and Purpose—

Intracerebral hemorrhage has no effective treatment. The delayed appearance of edema, apoptosis, and inflammation in perihematomal brain suggests that these events may be targets for therapeutic intervention. To develop successful treatments, we must learn more about the effects of hemorrhage on brain tissue. In this study, we investigated the acute metabolic effects of intrastriatal hemorrhage in rat brain.

Methods—

Lysed blood or saline (50 μL each) was injected into the striatum of male Sprague-Dawley rats. The rats recovered for 1 to 72 hours before injection of [
14
C]-2-deoxyglucose (intraperitoneally) 30 minutes before decapitation. Animals were pretreated with the
N
-methyl-
d
-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonists dizolcilpine maleate (MK-801; 1 mg/kg) or 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo[
f
]quinoxaline (NBQX; 30 mg/kg), or saline vehicle. Additional animals received intrastriatal injections of glutamate (1.0 mmol/L), NMDA (1.0 mmol/L), or AMPA (0.1 mmol/L) in the place of blood. Semiquantitative autoradiographs from the brains were analyzed to determine the effects of hemorrhage on relative glucose metabolism.

Results—

We found an acute phase of increased [
14
C]-2-deoxyglucose uptake in the perihematomal region that peaks 3 hours after lysed blood injection. Saline injections had no effect on striatal glucose utilization. The increased [
14
C]-2-deoxyglucose uptake produced by the hemorrhages was blocked by pretreatment with MK-801 and NBQX. Glutamate injections alone had no effect on striatal metabolism, whereas NMDA and AMPA injections increased [
14
C]-2-deoxyglucose uptake.

Conclusions—

The data imply that glutamate activation of NMDA or AMPA receptors increases glucose metabolism in perihematomal brain at early times after intracerebral hemorrhage. This may provide a possible target for the treatment of intracerebral hemorrhage.
Modification of Endothelial NO Synthase Through Protein Phosphorylation After Forebrain Cerebral Ischemia/Reperfusion
Authors: Osuka Koji , Watanabe Yasuo , Usuda Nobuteru , Nakazawa Ayami , Tokuda Masaaki , Yoshida Jun
Published: September 2004

Background and Purpose—

Production of NO by endothelial NO synthase (eNOS) is thought to play a neuroprotective role after cerebral ischemia. The vascular endothelial growth factor (VEGF) contributes to activation of eNOS by Ca
2+
/calmodulin and also stimulates the protein kinase Akt, which directly phosphorylates eNOS on Ser
1177
and increases enzyme activity. Although the expression of VEGF has been studied in ischemic stroke models, the activation of eNOS after cerebral ischemia has not been investigated. The purpose of the present study was to clarify molecular mechanisms underlying the regulation of eNOS activity through protein phosphorylation in postischemic processes.

Methods—

Sprague-Dawley rats were subjected to forebrain cerebral ischemia for 15 minutes with hypotension and reperfusion for up to 24 hours. Western blot analysis and ELISAs were used to study the temporal profiles of Akt, phospho-Akt at Ser
437
, eNOS, phospho-eNOS at Ser
1177
, and VEGF expression, respectively. Immunohistochemical studies were performed to examine the spatial expression patterns of phospho-Akt at Ser
437
and phospho-eNOS at Ser
1177
.

Results—

Increase in phospho-Akt at Ser
437
was observed transiently 0.5 to 2 hours after reperfusion, whereas elevation of phospho-eNOS at Ser
1177
and VEGF expression was observed from 6 hours after reperfusion. Endothelial cells in the microvessels were the major source of eNOS phosphorylated at Ser
1177
at the 12-hour time point.

Conclusions—

Increase in Ser
1177
phospho-eNOS occurs in endothelial cells of microvessels after ischemic episodes with temporal expression of VEGF, pointing to a contribution to the autoregulation of postischemic brain damage.
Diffusion-Weighted MRI in 300 Patients Presenting Late With Subacute Transient Ischemic Attack or Minor Stroke
Authors: Schulz Ursula G. , Briley Dennis , Meagher Tom , Molyneux Andrew , Rothwell Peter M.
Published: September 2004

Background and Purpose—

Many patients with transient ischemic attack (TIA) or minor stroke present to medical attention after a delay of several days or weeks, at which time it may be more difficult to obtain a clear history and clinical signs may have resolved. Because ischemic lesions on diffusion-weighted MRI (DWI) often persist for several weeks, we hypothesized that adding DWI to a standard protocol with T2-weighted imaging might be useful in the management of patients presenting late.

Methods—

We studied consecutive patients with TIA or minor stroke presenting ≥3 days after the event. Two independent observers recorded the presence or absence of recent ischemic lesions on 2 different occasions, first with the T2 scan only, and second with T2 and DWI. Each time, with the aid of a written clinical summary, the observers recorded their diagnosis and proposed management.

Results—

300 patients (159 men) were scanned at a median of 17 (interquartile range=10 to 23) days after symptom onset. DWI showed a high signal lesion in 114/164 (70%) minor strokes versus 17/136 (13%) TIAs (
P
<0.0001). The presence of high-signal lesions on DWI decreased nonlinearly with time since symptom onset (
P
<0.0001) and increased with National Institutes of Health Stroke Score (
P
=0.038) and with age (
P
=0.01). In 90/206 (43.7%) patients with 1 or multiple lesions on T2, DWI helped to clarify whether these were related to a recent ischemic event (79 [48%] strokes; 11 [31%] TIAs). Compared with T2 alone, DWI provided additional information in 108 (36%) patients (91 [56%] strokes and 17 [13%] TIAs), such as clarification of clinical diagnosis (18 patients, 6%) or vascular territory (28 patients, 9.3%), which was considered likely to influence management in 42 (14%) patients (32 [19%] strokes; 10 [7.4%] TIAs).

Conclusions—

The clinically useful information available from DWI provides a further justification for an MRI-based imaging protocol in patients with subacute TIA or minor stroke.
Cortical Regions for Judgments of Emotions and Personality Traits from Point-light Walkers
Authors: Heberlein Andrea S. , Adolphs Ralph , Tranel Daniel , Damasio Hanna
Published: September 2004

Humans are able to use nonverbal behavior to make fast, reliable judgments of both emotional states and personality traits. Whereas a sizeable body of research has identified neural structures critical for emotion recognition, the neural substrates of personality trait attribution have not been explored in detail. In the present study, we investigated the neural systems involved in emotion and personality trait judgments. We used a type of visual stimulus that is known to convey both emotion and personality information, namely, point-light walkers. We compared the emotion and personality trait judgments made by subjects with brain damage to those made by neurologically normal subjects and then conducted a lesion overlap analysis to identify neural regions critical for these two tasks. Impairments on the two tasks dissociated: Some subjects were impaired at emotion recognition, but judged personality normally; other subjects were impaired on the personality task, but normal at emotion recognition. Moreover, these dissociations in performance were associated with damage to specific neural regions: Right somatosensory cortices were a primary focus of lesion overlap in subjects impaired on the emotion task, whereas left frontal opercular cortices were a primary focus of lesion overlap in subjects impaired on the personality task. These findings suggest that attributions of emotional states and personality traits are accomplished by partially dissociable neural systems.
Anticipating Words and Their Gender: An Event-related Brain Potential Study of Semantic Integration, Gender Expectancy, and Gender Agreement in Spanish Sentence Reading
Authors: Wicha Nicole Y. Y. , Moreno Eva M. , Kutas Marta
Published: September 2004

Recent studies indicate that the human brain attends to and uses grammatical gender cues during sentence comprehension. Here, we examine the nature and time course of the effect of gender on word-by-word sentence reading. Event related brain potentials were recorded to an article and noun, while native Spanish speakers read medium to high-constraint Spanish sentences for comprehension. The noun either fit the sentence meaning or not, and matched the preceding article in gender or not; in addition, the preceding article was either expected or unexpected based on prior sentence context. Semantically anomalous nouns elicited an N400. Gender disagreeing nouns elicited a posterior late positivity (P600), replicating previous findings for words. Gender agreement and semantic congruity interacted in both the N400 window—with a larger negativity frontally for double violations—and the P600 window—with a larger positivity for semantic anomalies, relative to the prestimulus baseline. Finally, unexpected articles elicited an enhanced positivity (500–700 msec post onset) relative to expected articles. Overall, our data indicate that readers anticipate and attend to the gender of both articles and nouns, and use gender in real time to maintain agreement and to build sentence meaning.
Deficits for Semantics and the Irregular Past Tense: A Causal Relationship?
Authors: Tyler Lorraine K. , Stamatakis Emmanuel A. , Jones Roy W. , Bright Peter , Acres Kadia , Marslen-Wilson William D.
Published: September 2004

The regular and irregular past tense has become a focus for recent debates about the structure of the language processing system, asking whether language functions are subserved by different neural and functional mechanisms or whether all processes can be accommodated within a single unified system. A critical claim of leading single mechanism accounts is that the relationship between an irregular stem and its past tense form is primarily semantic and not morphological in nature. This predicts an obligatory relationship between semantic performance and access to the irregular past tense, such that a semantic deficit necessarily leads to impairments on the irregulars. We tested this claim in a series of studies probing the comprehension and production of regular and irregular past tense forms in four semantic dementia patients, all of whom had profound semantic deficits. In two elicitation tasks and one auditory priming study, we found that three out of the four patients did not have a deficit for the irregular past tense, in spite of their semantic deficits. This argues against the view that the relationship between irregular past tense forms and their stems is primarily semantic, and more generally against the single system claim that morphological structure can be captured solely based on phonological and semantic relationships.
French Cinema’s New ‘Sexual Revolution’: Postmodern Porn and Troubled Genre
Authors: Downing Lisa
Published: September 2004

This article proposes and examines a selection of interpretative strategies for viewing the type of sexually explicit art film made by French directors Catherine Breillat, Patrice Chéreau, Gaspar Noé and the team Virginie Despentes and Coralie Trinh Thi, over the past five years. To contextualise the relevant debates, political work on pornography, produced mainly by feminists in the 1970s and 1980s, is placed in dialogue with recent deconstructive gender theory and postmodern philosophy. While this hybridisation of theory problematises what pornography is, my readings of the films demonstrate that the cinematic medium may call into question our habitual ways of seeing sexuality. This is done by means of denaturalisation of the sexual spectacle ( Romance, 1999) or generic collage and the dislocation of ideology from genre ( Baise-moi, 2001; Irréversible2002). I conclude that, rather than being pornographic films, these problematic works constitute specifically cinematic interventions into wider contemporary cultural debates about the status of gender, sexuality and subjecthood at the turn of the twenty-first century.
Do Electrons Have Politics? Constructing User Identities in Swedish Electricity
Authors: Summerton Jane
Published: September 2004

Electricity systems in many parts of Europe and the United States are currently undergoing transformations that have potentially profound implications for managerial practice and the politics of user identities within these systems. After more than a century of “universal service” that provided technical goods and services to all users on essentially equal terms, utility managers are now constructing and exploiting heterogeneity and difference among users. This article explores local managerial practices within Swedish electricity in the mid-1990s, where managers promoted “brand-name” electricity as a strategy for configuring identities for users, their utilities, and electricity itself. These dynamics are analyzed using theoretical perspectives from two bodies of science and technology studies on configuring users’ identities. The article then analyzes the emergent practices and their theoretical and political implications for understanding of how and why artifacts, users, and organizational entities are coconstituted in ongoing technoscientific practice in infrastructural systems.
The Relationship between Gender and Topic in Gender-Preferential Language Use
Authors: Janssen Anna , Murachver Tamar
Published: September 2004

This study investigates the roles of biological and psychological gender, as well as assigned discussion topic, in the written language use of nonprofessional writers. University students wrote passages on three specific topics—one socioemotional and descriptive, one functional, and one involving political debate. Effects of biological gender were minimal. Psychological gender played a greater role, particularly when measured explicitly rather than implicitly. Passage topic played the greatest role in language use. Rather than enacting their own gender through their writing, writers used language befitting the passage topic. More female-preferential devices featured in passages involving socioemotional descriptions and more male-preferential features were employed in passages involving political debate. The study demonstrates the relative impacts of gender and contextual constraints on communication.
High School Students’ Compositions of Ranch Designs
Authors: Smagorinsky Peter , Pettis Victoria , Reed Patty
Published: September 2004

This research analyzed the composing processes of two high school students designing horse ranch plans for a course in equine management and production. The investigation focused on understanding the problems driving the design process, the tools through which the students inscribed and encoded meaning in their compositions, and the integration, representation, and mediation of their emerging identities through the design process. The analysis revealed that the students solved problems suggested by the particular culture surrounding the production of a specific breed of horse and constructed unique problems based on their knowledge of horses and ranch facilities. The tools through which they constructed these texts suggested both the cultural dimensions and narrative inscriptions of their designs. The culturally mediated narratives in particular contributed to students’ construction of identities, especially with respect to their orientation as members of the managerial (Darin) and working (Riley) classes.
Differential Corticomotor Control of a Muscle Adjacent to a Painful Joint
Authors: On Arzu Yağiz , Uludağ Burhanettin , Taşkiran Emin , Ertekin Cumhur
Published: September 2004

Objective. To assess the effects of chronic knee pain on neural control of the nearby quadriceps muscle. Methods. Motor-evoked potentials (MEP) in response to transcranial magnetic stimulation (TMS) of the motor cortex, maximal M responses, patellar tendon responses, and EMG activity during maximal isometric contraction were recorded from the right vastus medialis oblique (VMO) and vastus lateralis (VL) muscles in 13 patients with chronic patellofemoral pain syndrome (PPS) and 13 healthy volunteers. MEP and maximal M responses were also recorded from the right extensor digitorum brevis (EDB) muscle. Results. MEP amplitudes from VMO and VL were larger in patients with PPS than in controls. On the other hand, maximal M responses, EMG activity with maximal voluntary contraction, and tendon responses were smaller in patients than in controls. Motor-evoked responses and maximal M responses of the EDB muscle did not show significant difference between the 2 groups. Conclusions. These results indicate that chronic knee pain modulates central motor control of an adjacent muscle.
Posterior Alien Hand Syndrome: Case Report and Rehabilitative Treatment
Authors: Pappalardo A. , Ciancio M. R. , Reggio E. , Patti F.
Published: September 2004

Alien hand syndrome (AHS) is a rare syndrome characterized by involuntary, uncontrollable, and purposeless movement of one upper limb, which is considered as extraneous by the patient. The term AHS was previously used to describe a syndrome due to lesions in the anterior corpus callosum. Successively, some authors reported cases of AHS in patients due to posterior cerebral lesions, without lesions of the corpus callosum. Thus, it was possible to distinguish the posterior variant of AHS from the anterior form. The authors report an unusual case of posterior AHS due to a unique parieto-occipital lesion of the dominant hemisphere. However, the patient showed clinical findings that were similar to the anterior AHS. The rehabilitative treatment, individualized and targeted toward the specific needs of the patient, allowed the improvement of the patient’s participation in activities of daily living.
Competitive clonal hematopoiesis in mouse chimeras explained by a stochastic model of stem cell organization
Authors: Roeder Ingo , Kamminga Leonie M. , Braesel Katrin , Dontje Bert , de Haan Gerald , Loeffler Markus
Published: September 2004

Many current experimental results show the necessity of new conceptual approaches to understand hematopoietic stem cell organization. Recently, we proposed a novel theoretical concept and a corresponding quantitative model based on microenvironment-dependent stem cell plasticity. The objective of our present work is to subject this model to an experimental test for the situation of chimeric hematopoiesis. Investigating clonal competition processes in DBA/2-C57BL/6 mouse chimeras, we observed biphasic chimerism development with initially increasing but long-term declining DBA/2 contribution. These experimental results were used to select the parameters of the mathematical model. To validate the model beyond this specific situation, we fixed the obtained parameter configuration to simulate further experimental settings comprising variations of transplanted DBA/2-C57BL/6 proportions, secondary transplantations, and perturbation of stabilized chimeras by cytokine and cytotoxic treatment. We show that the proposed model is able to consistently describe the situation of chimeric hematopoiesis. Our results strongly support the view that the relative growth advantage of strain-specific stem cells is not a fixed cellular property but is sensitively dependent on the actual state of the entire system. We conclude that hematopoietic stem cell organization should be understood as a flexible, self-organized rather than a fixed, preprogrammed process.
Circulating endothelial cells, von Willebrand factor, interleukin-6, and prognosis in patients with acute coronary syndromes
Authors: Lee Kaeng W. , Lip Gregory Y. H. , Tayebjee Muzahir , Foster William , Blann Andrew D.
Published: September 2004

Markers of inflammation (eg, interleukin-6 [IL-6]), and endothelial perturbation (von Willebrand factor [VWF], circulating endothelial cells [CECs]) are altered in acute coronary syndromes (ACS). We hypothesized that CECs and IL-6 levels during the first 48 hours of ACS would predict 30-day and 1-year major cardiovascular end points (MACE). A total of 156 patients with ACS were included. Blood was drawn on admission (baseline) and 48 hours later for plasma VWF, IL-6 (both enzyme-linked immunosorbent assay [ELISA]), and CECs (CD146 immunomagnetic separation). CEC phenotyping was performed by indirect immunoperoxidase staining. At 30 days, 48 patients had a MACE, a predicted by baseline and 48-hour CECs and IL-6 levels, 48-hour VWF levels, and by the “admission–48 hour change” (Δ) in CECs, VWF, and IL-6 (all P = .002). On multivariate analysis, 48-hour CECs (P < .001) were the strongest predictor of MACE, followed by ΔIL-6 (P = .01) and ΔVWF (P = .048); 48-hour CECs were the only predictor of death (P = .007). At 1 year, 65 patients had MACE, predicted by 48-hour CECs and ΔIL-6 levels (P < .001); age (P = .046) and 48-hour CECs (P < .001) were the only predictors of death. CECs stained 93% positive for endothelial nitric oxide synthase (eNOS) but were less than 1% positive for CD34, CD36, and CD45 and less than 3% for CD31. Like raised VWF, abnormal CECs and IL-6 levels during the first 48 hours of ACS were strongly associated with 30-day MACE. CECs at 48 hours were the only independent predictor of both death and MACE at 30 days and 1 year, indicating the crucial role of endothelial/vascular damage in ACS pathophysiology.
HCV quasispecies evolution: association with progression to end-stage liver disease in hemophiliacs infected with HCV or HCV/HIV
Authors: Qin Hongxing , Shire Norah J. , Keenan Erica D. , Rouster Susan D. , Eyster M. Elaine , Goedert James J. , Koziel Margaret James , Sherman Kenneth E. ,   and the Multicenter Hemophilia Cohort Study Group
Published: September 2004

Patients with inherited bleeding disorders who received clotting factor concentrates before 1987 have high rates of hepatitis C virus (HCV) or HCV/HIV infection. We evaluated HCV quasispecies evolution in longitudinally collected specimens comparing those from patients with progression to end-stage liver disease (ESLD; cases) to those with compensated chronic hepatitis (controls). Plasma samples were obtained from the National Cancer Institute Multicenter Hemophilia Cohort Study. Controls were matched for age, sex, infection duration, and presence/absence of HIV. Samples from early infection were compared to those obtained after onset of ESLD in the cases. The first hypervariable (HVR1) and core proteincoding regions were amplified, subcloned, and sequenced. Complexity and diversity were determined. More than 700 sub-clones from 10 pairs of patients (8 with HIV) followed over approximately 9.3 years were evaluated. HVR1 complexity narrowed over time in the cases, whereas it increased in controls (P = .01). Similar trends were observed for diversity within HVR1 and the core region (P = .04). HCV-infected patients with inherited bleeding disorders undergo quasispecies evolution over time. Evolution patterns differ for progressors and nonprogressors. Further understanding of these mechanisms may help identify factors related to progression rate and treatment response.
Human embryonic stem cell–derived CD34+ cells: efficient production in the coculture with OP9 stromal cells and analysis of lymphohematopoietic potential
Authors: Vodyanik Maxim A. , Bork Jack A. , Thomson James A. , Slukvin Igor I.
Published: September 2004

Embryonic stem (ES) cells have the potential to serve as an alternative source of hematopoietic precursors for transplantation and for the study of hematopoietic cell development. Using coculture of human ES (hES) cells with OP9 bone marrow stromal cells, we were able to obtain up to 20% of CD34+ cells and isolate up to 107 CD34+ cells with more than 95% purity from a similar number of initially plated hES cells after 8 to 9 days of culture. The hES cell–derived CD34+ cells were highly enriched in colony-forming cells, cells expressing hematopoiesis-associated genes GATA-1, GATA-2, SCL/TAL1, and Flk-1, and retained clonogenic potential after in vitro expansion. CD34+ cells displayed the phenotype of primitive hematopoietic progenitors as defined by co-expression of CD90, CD117, and CD164, along with a lack of CD38 expression and contained aldehyde dehydrogenase–positive cells as well as cells with verapamil-sensitive ability to efflux rhodamine 123. When cultured on MS-5 stromal cells in the presence of stem cell factor, Flt3-L, interleukin 7 (IL-7), and IL-3, isolated CD34+ cells differentiated into lymphoid (B and natural killer cells) as well as myeloid (macrophages and granulocytes) lineages. These data indicate that CD34+ cells generated through hES/OP9 coculture display several features of definitive hematopoietic stem cells.
Induction of BCR-ABL–specific immunity following vaccination with chaperone-rich cell lysates derived from BCR-ABL+ tumor cells
Authors: Zeng Yi , Graner Michael W. , Thompson Sylvia , Marron Marilyn , Katsanis Emmanuel
Published: September 2004

We have previously reported that chaperonerich cell lysates (CRCL) derived from the BCR-ABL+ 12B1 leukemia activate dendritic cells (DCs) and stimulate leukemia-specific immune responses. Because CRCL contain a variety of heat shock/chaperone proteins, we theorized that CRCL obtained from BCR-ABL+ leukemias are likely to chaperone BCR-ABL–derived fusion peptides and that DCs pulsed with 12B1 CRCL could cross-present BCR-ABL fusion peptides to T cells. We found that splenocytes from mice vaccinated with BCR-ABL+ leukemia-derived CRCL secreted interferon-γ (IFN-γ) when restimulated with a BCR-ABL peptide, GFKQSSKAL, indicating that BCR-ABL peptides are chaperoned by leukemia-derived CRCL. We next eluted peptides from 12B1 leukemia-derived CRCL and used high-pressure liquid chromatography (HPLC) fractions to restimulate splenocytes harvested from mice vaccinated with DC/GFKQSSKAL or DC/12B1 CRCL. We found that the same peptide fractions derived from 12B1 CRCL and from “refractionated” GFKQSSKAL stimulated IFN-γ production, suggesting the presence of BCR-ABL peptides in the peptide repertoire of 12B1 CRCL. We also demonstrated that immunization with DCs loaded with leukemia-derived CRCL induced BCR-ABL–specific cytotoxic T lymphocytes (CTLs) in vivo. Moreover, mice immunized with DCs pulsed with 12B1-derived CRCL had superior survival (60%) when compared with those immunized with DCs pulsed with BCR-ABL peptide (20%), indicating that CRCL vaccines provide additional immune stimulus over and above individual peptide vaccination.