bluuebunny/crossref_metadata_2025 huggingface dataset:
Mouse Genetic Evidence That Tranilast Reduces Smooth Muscle Cell Hyperplasia via a p21
WAF1
-Dependent Pathway
Authors: Sata Masataka , Takahashi Akihiro , Tanaka Kimie , Washida Miwa , Ishizaka Nobukazu , Ako Junya , Yoshizumi Masao , Ouchi Yasuyoshi , Taniguchi Takahiro , Hirata Yasunobu , Yokoyama Mitsuhiro , Nagai Ryozo , Walsh Kenneth
Published: October 2002

Objective—

N
-(3′4′-dimethoxycinnamoyl)-anthranilic acid (tranilast) is a drug that has been shown to reduce the incidence of restenosis after angioplasty in middle-scale clinical trials. Despite clinical interest in this drug, the pharmacological actions of tranilast remain relatively unexplored at a molecular level.

Methods and Results—

We evaluated the effects of tranilast on vascular smooth muscle cell (VSMC) proliferation in wild-type mice and in mice lacking a cyclin-dependent kinase inhibitor, p21
WAF1
(p21). Tranilast potently inhibited the proliferation of VSMC cultures derived from wild-type mice, but VSMCs derived from p21-deficient (p21−/−) mice were unaffected by this treatment. In a mouse femoral artery model of vascular injury, tranilast administration to wild-type mice led to an upregulation of p21 expression and a decrease in the number of proliferating VSMCs, as determined by immunostaining for proliferating cell nuclear antigen. In contrast, tranilast had no effect on the number of proliferating cell nuclear antigen–positive cells in the injured arteries of p21−/− mice. Administration of tranilast significantly reduced the neointimal VSMC hyperplasia in wild-type mice at 4 weeks but had no effect on lesion formation in p21−/− mice.

Conclusions—

Our findings provide genetic evidence that tranilast inhibits intimal hyperplasia via a p21-dependent pathway, an activity that may contribute to its efficacy in the prophylactic treatment of postangioplasty restenosis.
Two-Year Angiographic Follow-Up of Intracoronary Sr90 Therapy for Restenosis Prevention After Balloon Angioplasty
Authors: Meerkin David , Joyal Michel , Tardif Jean-Claude , Lespérance Jacques , Arsenault André , Lucier Guylaine , Bonan Raoul
Published: October 2002

Background

—

Postcoronary angioplasty vascular brachytherapy (VBT) has emerged as a successful intervention for restenosis prevention in some clinical scenarios. Longer-term follow-up after VBT in de novo nonstented lesions has not been reported.

Methods and Results

—

Thirty patients treated with post–percutaneous transluminal coronary angioplasty (PTCA) VBT with Sr
90
underwent clinical and angiographic follow-up at 6 and 24 months. Specific vessel segment quantitative coronary angiographic analyses were performed to identify radiation edge effects. Nineteen patients who had not undergone index procedure stenting or target vessel revascularization (TVR) over the 2-year period were analyzed separately. Of the 30 patients, 3 underwent TVR by 6-month follow-up. An additional 4 patients required TVR between 6 and 24 months. In the total cohort of 26 patients undergoing angiographic follow-up at 6 and 24 months, an increase in minimal lumen diameter of the initial target segment was noted at 6 months compared with postprocedure analysis (2.31±0.48 versus 2.04±0.43 mm,
P
<0.05). At 24 months, this was no longer significant (2.19±0.61 mm). In the proximal segments of the entire cohort and the nonintervened subgroup, the principal late loss occurred over the first 6 months with no additional late loss at 2-year follow-up. The distal segments remained stable over the entire follow-up period.

Conclusions

—

Although some late failures of post-PTCA VBT are seen between 6 and 24 months, most treated vessels remain stable with no late loss or additional luminal increase beyond the 6-month period. This suggests that late aneurysm formation and significant late edge restenosis are unlikely in VBT after PTCA of de novo lesions for up to 2 years.
Clinical Determinants of Ventricular Sympathetic Reinnervation After Orthotopic Heart Transplantation
Authors: Bengel Frank M. , Ueberfuhr Peter , Hesse Thomas , Schiepel Nina , Ziegler Sibylle I. , Scholz Siegfried , Nekolla Stephan G. , Reichart Bruno , Schwaiger Markus
Published: October 2002

Background—

It has been demonstrated that ventricular sympathetic reinnervation after cardiac transplantation improves exercise performance. The extent of reinnervation increases with time but is variable. Little is known about other influencing factors.

Methods and Results—

Seventy-seven nonrejecting transplant recipients were cross-sectionally studied by PET with the catecholamine analogue C-11 hydroxyephedrine at 4.8±3.5 years after transplantation. Results were compared with history-derived parameters related to recipient’s clinical course before, during, and after surgery; donor characteristics; and immunogenetics. Partial reinnervation was observed in 52 patients (extent, 21±16% of left ventricle). Complete denervation was found in 25 patients at various times after transplantation. Reinnervation extent correlated with time after surgery (
r
=0.387;
P
<0.001) but also inversely with donor age (
r
=−0.309,
P
=0.006) and recipient age (
r
=−0.243,
P
=0.032). Maximal hydroxyephedrine retention correlated inversely with frequency of rejection episodes (
r
=−0.267,
P
=0.019), was reduced when aortic complications occurred perioperatively (9 patients), and correlated inversely with aortic cross-clamp time (
r
=−0.331,
P
=0.006). Other parameters were not associated with reinnervation. Patients were surveyed for clinical complications over >12 months after PET (until 7.3±4.2 years after transplantation), but significant effects of reinnervation on outcome were not observed.

Conclusions—

The present data suggest that sympathetic reinnervation after cardiac transplantation is not simply a function of time. Reinnervation is more likely with young age, fast and uncomplicated surgery, and low rejection frequency. Despite few effects on prognosis in otherwise healthy recipients, improved understanding of clinical determinants may contribute to enhance allograft reinnervation and thereby augment exercise capacity in the future.
Ultrasonic Characterization of the Pulmonary Venous Wall
Authors: Cabrera José Angel , Sánchez-Quintana Damián , Farré Jerónimo , Navarro Felipe , Rubio José Manuel , Cabestrero Fernando , Anderson Robert H. , Ho Siew Yen
Published: October 2002

Background—

Pulmonary vein isolation with radiofrequency catheter ablation techniques is used to prevent recurrences of human atrial fibrillation. Visualization of the architecture at the venoatrial junction could be crucial for these ablative techniques. Our study assesses the potential for intravascular ultrasound to provide this information.

Methods and Results—

We retrieved 32 pulmonary veins from 8 patients dying from noncardiac causes. We obtained cross-sectional intravascular ultrasound (IVUS) images with a 3.2F, 30-MHz ultrasound catheter at intervals on each vein. Histological cross-sections at the intervals allowed comparisons with ultrasonic images. The pulmonary venous wall at the venoatrial junction revealed a 3-layered ultrasonic pattern. The inner echogenic layer represents both endothelium and connective tissue of the media (mean maximal thickness, 1.4±0.3 mm). The middle hypoechogenic stratum corresponds to the sleeves of left atrial myocardium surrounding the external aspect of the venous media. This layer was thickest at the venoatrial junction (mean maximal thickness, 2.6±0.8 mm) and decreased toward the lung hilum. The outer echodense layer corresponds to fibro-fatty adventitial tissue (mean maximal thickness, 2.15±0.36 mm). We found a close agreement among the IVUS and histological measurements for maximal luminal diameter (mean difference, −0.12±1.3 mm) and maximal muscular thickness (mean difference, 0.17±0.13 mm) using the Bland and Altman method.

Conclusions—

Our experimental study demonstrates for the first time that IVUS images of the pulmonary veins can provide information on the distal limits and thickness of the myocardial sleeves and can be a valuable tool to help accurate targeting during ablative procedures.
Decrease in Renal Medullary Endothelial Nitric Oxide Synthase of Fructose-Fed, Salt-Sensitive Hypertensive Rats
Authors: Nishimoto Yasuhiro , Tomida Takahito , Matsui Hideo , Ito Takayuki , Okumura Kenji
Published: October 2002

We investigated the expression of endothelial NO synthase (eNOS) in the kidneys of fructose-fed insulin-resistant rats (FFR) with a low- or high-sodium diet. Male Sprague-Dawley rats were fed a control (C) or high-fructose (40% fructose; F) diet, with each coming in low-sodium (0.024% NaCl; LS-C or LS-F) or high-sodium (3% NaCl; HS-C or HS-F) varieties, for 2 weeks. Half of the FFR were orally administered pioglitazone (10 mg · kg
−1
· day
−1
), an insulin-sensitizing agent (LS-FP or HS-FP). The systolic blood pressure was significantly higher in the HS-F rats than in the LS-F rats or the HS-C rats (HS-F rats, 129±4 mm Hg, versus LS-F rats, 115±3 mm Hg,
P
<0.05; or versus HS-C rats, 116±5 mm Hg,
P
<0.05), which indicated the salt dependence of hypertension in FFR. The protein expression of eNOS in the renal medulla of FFR was significantly lower than that in control rats during a high sodium load. The administration of pioglitazone prevented the hypertension (HS-F rats, 129±4 mm Hg, versus HS-FP rats, 113±3 mm Hg,
P
<0.05) and the reduction of medullary eNOS protein expression in HS-F rats. There was no significant difference in eNOS expression in the renal cortex or aorta between FFR and control rats, regardless of sodium load. These results suggest that the decrease in renal medullary NO production by eNOS during a high sodium load may play a role in fructose-fed, salt-sensitive hypertension.
Differentiation of Pluripotent Embryonic Stem Cells Into Cardiomyocytes
Authors: Boheler Kenneth R. , Czyz Jaroslaw , Tweedie David , Yang Huang-Tian , Anisimov Sergey V. , Wobus Anna M.
Published: October 2002

Embryonic stem (ES) cells have been established as permanent lines of undifferentiated pluripotent cells from early mouse embryos. ES cells provide a unique system for the genetic manipulation and the creation of knockout strains of mice through gene targeting. By cultivation in vitro as 3D aggregates called embryoid bodies, ES cells can differentiate into derivatives of all 3 primary germ layers, including cardiomyocytes. Protocols for the in vitro differentiation of ES cells into cardiomyocytes representing all specialized cell types of the heart, such as atrial-like, ventricular-like, sinus nodal–like, and Purkinje-like cells, have been established. During differentiation, cardiac-specific genes as well as proteins, receptors, and ion channels are expressed in a developmental continuum, which closely recapitulates the developmental pattern of early cardiogenesis. Exploitation of ES cell–derived cardiomyocytes has facilitated the analysis of early cardiac development and has permitted in vitro “gain-of-function” or “loss-of-function” genetic studies. Recently, human ES cell lines have been established that can be used to investigate cardiac development and the function of human heart cells and to determine the basic strategies of regenerative cell therapy. This review summarizes the current state of ES cell–derived cardiogenesis and provides an overview of how genomic strategies coupled with this in vitro differentiation system can be applied to cardiac research.
Na
+
-Ca
2+
Exchange Activity Is Localized in the T-Tubules of Rat Ventricular Myocytes
Authors: Yang Z. , Pascarel C. , Steele D.S. , Komukai K. , Brette F. , Orchard C.H.
Published: October 2002

Detubulation of rat ventricular myocytes has been used to investigate the role of the t-tubules in Ca
2+
cycling during excitation-contraction coupling in rat ventricular myocytes. Ca
2+
was monitored using fluo-3 and confocal microscopy. In control myocytes, electrical stimulation caused a spatially uniform increase in intracellular [Ca
2+
] across the cell width. After detubulation, [Ca
2+
] rose initially at the cell periphery and then propagated into the center of the cell. Application of caffeine to control myocytes resulted in a rapid and uniform increase of intracellular [Ca
2+
]; the distribution and amplitude of this increase was the same in detubulated myocytes, although its decline was slower. On application of caffeine to control cells, there was a large, rapid, and transient rise in extracellular [Ca
2+
] as Ca
2+
was extruded from the cell; this rise was significantly smaller in detubulated cells, and the remaining increase was blocked by the sarcolemmal Ca
2+
ATPase inhibitor carboxyeosin. The treatment used to produce detubulation had no significant effect on Ca
2+
efflux in atrial cells, which lack t-tubules. Detubulation of ventricular myocytes also resulted in loss of Na
+
-Ca
2+
exchange current, although the density of the fast Na
+
current was unaltered. It is concluded that Na
+
-Ca
2+
exchange function, and hence Ca
2+
efflux by this mechanism, is concentrated in the t-tubules, and that the concentration of Ca
2+
flux pathways in the t-tubules is important in producing a uniform increase in intracellular Ca
2+
on stimulation.
Life Span of Ventricular Fibrillation Frequencies
Authors: Choi Bum-Rak , Nho Wonchul , Liu Tong , Salama Guy
Published: October 2002

The nature and organization of electrical activity during ventricular fibrillation (VF) are important and controversial subjects dominated by 2 competing theories: the wavebreak and the dominant mother rotor hypothesis. To investigate spatiotemporal characteristics of ventricular fibrillation (VF), transmembrane potentials (V
m
) were recorded from multiple sites of perfused rabbit hearts using a voltage-sensitive dye and a photodiode array or a CCD camera, and the time-frequency characteristics of V
m
were analyzed by short-time fast Fourier transform (FFT) or generalized time-frequency representation with a cone-shaped kernel. The analysis was applied to all pixels to track VF frequencies in time and space. VF consisted of blobs, which are groups of contiguous pixels with a common frequency and an ill-defined shape. At any time
t
, several VF frequency blobs coexisted in the field of view, and the number of coexisting blobs was on average 5.9±2.1 (n=8 hearts) as they appeared and disappeared discontinuously with time and were not fixed in space. The life span of frequency blobs from birth to either annihilation or breakup to another frequency had a half-life of 0.39±0.13 second (n=4 hearts). The Ca
2+
channel blocker nifedipine increased the stability of VF frequencies and reduced the number of frequency blobs progressing to a single frequency. In conclusion, VF consists of dynamically changing frequency blobs, which have a short life span and can be modified by pharmacological interventions, suggesting that VF is maintained by dynamically changing multiple wavelets.
Clinical and Vascular Outcome in Internal Carotid Artery Versus Middle Cerebral Artery Occlusions After Intravenous Tissue Plasminogen Activator
Authors: Linfante Italo , Llinas Rafael H. , Selim Magdy , Chaves Claudia , Kumar Sandeep , Parker Robert A. , Caplan Louis R. , Schlaug Gottfried
Published: October 2002

Background and Purpose

—

Early reperfusion is a predictor of good outcome in acute ischemic stroke. We investigated whether middle cerebral artery (MCA) occlusions have a better clinical outcome and proportion of recanalization compared with internal carotid artery (ICA) occlusion after standard treatment with intravenous (IV) tissue plasminogen activator (tPA).

Patients

—

In a retrospective analysis of our prospective stroke database between January 7, 1998, and January 30, 2002, we identified 36 consecutive patients who were treated with IV tPA within 3 hours after symptom onset of a stroke in the distribution of a documented ICA or MCA occlusion. The National Institutes of Health Stroke Scale (NIHSS) score was recorded before tPA, at 24 hours, 3 days, and 3 months after stroke. Three-month outcome was recorded by modified Rankin scale. Magnetic resonance angiography or computed tomographic angiography was obtained before tPA. The presence of recanalization was assessed by transcranial Doppler and/or magnetic resonance angiography within 3 days after stroke onset.

Results

—

Nineteen patients had MCA occlusion, and 17 had ICA-plus-MCA occlusion before tPA. Although there was no difference in age and NIHSS at day 0 between the 2 groups, the MCA group had a lower day 3 NIHSS score compared with the ICA group (
P
=0.006) in an ANCOVA. In addition, patients who had a MCA occlusion had lower day 1 and 3 NIHSS scores compared with the ICA group (
P
=0.04 and
P
=0.03, respectively; Wilcoxon rank sum). Similarly, NIHSS was significantly lower in patients who recanalized on days 1 and 3 (
P
=0.004 and
P
=0.003 respectively, Wilcoxon rank sum). When we adjusted for NIHSS score at day 0 in an ANCOVA, the adjusted mean was lower in the group that recanalized compared with the group that did not recanalize (
P
<0.001). There was a significant difference between the proportion of recanalization in the MCA group (15 of 17 recanalized, 88%) at 3 days after tPA compared with that of the ICA group (5 of 16 recanalized, 31%;
P
=0.001, Fisher exact test). The 3-month modified Rankin scale was not different between the 2 groups.

Conclusions

—

Despite comparable age and NIHSS scores before IV tPA, MCA occlusions have lower day 1 and 3 NIHSS scores and higher proportion of recanalization compared with ICA occlusions. A combined IV/intra-arterial or mechanical thrombolysis may be needed to achieve early recanalization in ICA occlusions.
Impact of Aortic Stiffness on Ischemic Stroke in Elderly Patients
Authors: Sugioka Kenichi , Hozumi Takeshi , Sciacca Robert R. , Miyake Yumiko , Titova Inna , Gaspard Gabrielle , Sacco Ralph L. , Homma Shunichi , Di Tullio Marco R.
Published: October 2002

Background and Purpose

—

Large atherosclerotic plaques in the aortic arch detected by transesophageal echocardiography (TEE) are associated with increased risk of ischemic stroke in the elderly. The atherosclerotic process also affects aortic distensibility, which can also be assessed by TEE. The purpose of this study was to evaluate the possible association of aortic stiffness by TEE with ischemic stroke in elderly patients.

Methods

—

We performed TEE in 40 consecutive elderly patients aged ≥55 years with acute ischemic stroke and in 42 consecutive control subjects aged ≥55 years. Aortic stiffness index β, which has been used in the literature to express the stiffness of the aortic wall, was calculated as follows: β=ln (systolic blood pressure/diastolic blood pressure)/([D
max
−D
min
]/D
min
), where ln is natural logarithm, D
max
is maximum aortic lumen diameter, and D
min
is minimum aortic lumen diameter by TEE. The association of index β with ischemic stroke was evaluated by logistic regression analysis after adjustment for potential confounders, including thickness of aortic arch plaques.

Results

—

Index β was significantly greater in stroke patients than in controls (9.7±5.0 versus 5.3±3.5;
P
<0.0001). When aortic plaque thickness and other stroke risk factors were entered in multivariate analysis, index β was found to be independently associated with ischemic stroke (odds ratio, 1.28 per unit increase; 95% CI, 1.10 to 1.52).

Conclusions

—

Aortic stiffness by TEE is associated with ischemic stroke, independent of thickness of aortic arch plaques and other stroke risk factors. This suggests that aortic stiffness by TEE may add prognostic information when assessing the risk of ischemic stroke in the elderly.
Hyperhomocyst(e)inemia and Risk of Ischemic Stroke Among Young Asian Adults
Authors: Tan Nigel Choon-Kiat , Venketasubramanian N. , Saw Seang-Mei , Tjia Helen Tjoei-Lian
Published: October 2002

Background and Purpose

—

Hyperhomocyst(e)inemia is emerging as a possible risk factor for stroke, possibly because of accelerated atherosclerosis. There are no previous publications evaluating homocyst(e)ine in young Asian ischemic stroke patients. We conducted a case-control study examining homocyst(e)ine, vitamin B
12
, and folate levels in young, first-ever Asian ischemic stroke patients.

Methods

—

We prospectively recruited 109 consecutive young (<50 years) first-ever hospitalized ischemic stroke patients and 88 age/gender-matched hospital-based controls during a period of 18 months. Prevalence of vascular risk factors was assessed; fasting homocyst(e)ine, vitamin B
12
, and folate were assayed. Stroke mechanisms were subtyped using TOAST study criteria.

Results

—

Mean age was 43.8 (cases) and 43.1 (controls) years; 71.6% were male (cases and controls). Diabetes mellitus, hypertension, and hyperlipidemia were significantly more prevalent in cases. Mean fasting homocyst(e)ine levels were significantly higher in cases (13.7 μmol/L, 95% CI: 12.7 to 14.9) than controls (10.8 μmol/L, 95% CI: 9.9 to 11.8,
P
<0.001). Mean vitamin B
12
levels were significantly lower in cases (299.5 pmol/L, 95% CI: 266.7 to 332.3) than controls (394.5 pmol/L, 95% CI: 357.9 to 431.0,
P
<0.001). Folate levels were not significantly different. Mean homocyst(e)ine levels were significantly elevated in large-artery strokes (16.9 μmol/L, 95% CI: 14.5 to 19.7,
P
<0.001) but not other stroke subtypes compared with controls. Compared with the lowest homocyst(e)ine quartile, the highest quartile was significantly associated with an adjusted odds ratio of 4.3 for ischemic stroke and 25.3 for large-artery stroke. Using a logistic regression model, the adjusted odds ratio was 5.17 (95% CI: 1.96 to 13.63,
P
=0.001) for every 1 μmol/L increase in log homocyst(e)ine.

Conclusions

—

Hyperhomocyst(e)inemia is an independent risk factor for ischemic strokes in young Asian adults. The relationship between increasing homocyst(e)ine and stroke risk is strong, graded, and significant. The association with large-artery strokes suggests that hyperhomocyst(e)inemia may increase stroke risk via a proatherogenic effect.
Chaos and Form: A Sculptor's Sources in Science
Authors: Tacha Athena
Published: October 2002

In the 1960s the author sought to rethink the basic concepts of sculpture-space, matter, gravity and light-by studying the theories of relativity and quantum physics, the connection of space to time and matter to energy, and the relationship of all these to gravity. Subsequently, trying to understand the fundamental forms in nature, she discovered a continuity underlying them: Spirals are not only forms of growth or turbulence, but are also the link between spheres (forms of balance and minimum volume/energy) and waves (forms of energy/motion). Flow phenomena shaped the new style of her landscape sculptures, which are expressions of fluid dynamics and other nonlinear processes.
Schizophrenia and Narrative in Artificial Agents
Authors: Sengers Phoebe
Published: October 2002

Artificial-agent technology has become commonplace in technical research from com-puter graphics to interface design and in popular culture through the Web and computer games. On the one hand, the population of the Web and our PCs with characters who reflect us can be seen as a humaniza-tion of a previously purely mechanical interface. On the other hand, the mechanization of subjectivity carries the danger of simply reducing the human to the machine. The author argues that predominant artificial intelligence (AI) ap-proaches to modeling agents are based on an erasure of subjectivity analogous to that which appears when people are subjected to institutionalization. The result is agent behavior that is fragmented, depersonalized, lifeless and incomprehensible. Approaching the problem using a hybrid of critical theory and AI agent technology, the author argues that agent behavior should be narratively under-standable; she presents a new agent architecture that struc-tures behavior to be comprehen-sible as narrative.
Near-Synonymy and Lexical Choice
Authors: Edmonds Philip , Hirst Graeme
Published: October 2002

We develop a new computational model for representing the fine-grained meanings of near-synonyms and the differences between them. We also develop a lexical-choice process that can decide which of several near-synonyms is most appropriate in a particular situation. This research has direct applications in machine translation and text generation.

We first identify the problems of representing near-synonyms in a computational lexicon and show that no previous model adequately accounts for near-synonymy. We then propose a preliminary theory to account for near-synonymy, relying crucially on the notion of granularity of representation, in which the meaning of a word arises out of a context-dependent combination of a context-independent core meaning and a set of explicit differences to its near-synonyms. That is, near-synonyms cluster together.

We then develop a clustered model of lexical knowledge, derived from the conventional ontological model. The model cuts off the ontology at a coarse grain, thus avoiding an awkward proliferation of language-dependent concepts in the ontology, yet maintaining the advantages of efficient computation and reasoning. The model groups near-synonyms into subconceptual clusters that are linked to the ontology. A cluster differentiates near-synonyms in terms of fine-grained aspects of denotation, implication, expressed attitude, and style. The model is general enough to account for other types of variation, for instance, in collocational behavior.

An efficient, robust, and flexible fine-grained lexical-choice process is a consequence of a clustered model of lexical knowledge. To make it work, we formalize criteria for lexical choice as preferences to express certain concepts with varying indirectness, to express attitudes, and to establish certain styles. The lexical-choice process itself works on two tiers: between clusters and between near-synonyns of clusters. We describe our prototype implementation of the system, called I-Saurus.
Searching with Unilateral Neglect
Authors: Pavlovskaya Marina , Ring Haim , Groswasser Zeev , Hochstein Shaul
Published: October 2002

We address two longstanding conflicts in the visual search and unilateral neglect literature by studying feature and conjunction search performance of neglect patients using laterally presented search arrays. The first issue relates to whether feature search is performed independently of attention, or rather requires “spread attention”. If feature search is “preattentive,” it should survive neglect. However, we find neglect effects for both feature and conjunction search, suggesting that feature search, too, has an attentional requirement. The second controversy refers to the space-or object-based nature of neglect following unilateral right-hemisphere parietal lobe damage. If neglect were a purely spatial phenomenon, then we would expect no detriment in performance in the right (nonneglect) field, and diminished performance for the whole left (neglect) field. On the other hand, if neglect were purely object-based, we would expect diminished performance on the left side of the search array, irrespective of its location in the visual field. We now demonstrate a combination of strong object-based and space-based neglect effects for conjunction search with laterally placed element arrays, suggesting that these two mechanisms work in tandem.
Performing the American Right: The Bakersfield Business Conference
Authors: Mason Jeffrey D.
Published: October 2002

Each year since 1985, the American Right has celebrated itself at the Bakersfield Business Conference. This political vaudeville, a latter-day Chautauqua, is theatre on a grand scale, a well-rehearsed extravaganza featuring former U.S. presidents, former heads of state, athletes, movie stars, and present-day CEOs.
The Simulated Emergence of Distributed Environmental Control in Evolving Microcosms
Authors: Downing Keith L.
Published: October 2002

This work continues investigation into Gaia theory [Lovelock, (1995) The ages of Gaia, Oxford University Press] from an artificial life perspective [Downing, (2000) in Proceedings of the 7th International Conference on Artificial Life, (pp. 90–99) MIT Press], with the aim of assessing the general compatibility of emergent distributed environmental control with conventional natural selection. Our earlier system, GUILD [Downing and Zvirinsky, (1999) Artificial Life, 5, 291–318], displayed emergent regulation of the chemical environment by a population of metabolizing agents, but the chemical model underlying those results was trivial, essentially admitting all possible reactions at a single energy cost. The new model, METAMIC, utilizes abstract chemistries that are both (a) constrained to a small set of legal reactions, and (b) grounded in basic fundamental relationships between energy, entropy, and biomass synthesis/breakdown.

To explore the general phenomena of emergent homeostasis, we generate 100 different chemistries and use each as the basis for several METAMIC runs, as part of aGaia hunt. This search discovers 20 chemistries that support microbial populations capable of regulating a physical environmental factor within their growth-optimal range, despite the extra metabolic cost. Case studies from the Gaia hunt illustrate a few simple mechanisms by which real biota might exploit the underlying chemistry to achieve some control over their physical environment. Although these results shed little light on the question of Gaia on Earth, they support the possibility of emergent environmental control at the microcosmic level.
Biblical Literature and the Emergence of Ancient Jewish Nationalism
Authors: Weeks Stuart
Published: October 2002

The post-exilic concept of Israel can usefully be understood as analogous to the modern concept of a nation, and the conclusions of modern nationalist studies applied to the study of its emergence. By providing an account of the past and authoritative delineations of the community, the existing biblical texts may have provided the focus for a new sense of identity, whatever their original purpose and relationship with historical events.
Apostrophic Desire and Parousia in the Apostle Paul's Epistles: A Derridean Proposal for Textual Interpretation
Authors: Curkpatrick Stephen
Published: October 2002

Paul's correspondence encounters the vicissitudes of a postal system that sets in motion several forms of differential experience between addressor and addressee. In Paul's epistles, desire for his own parousia (coming/presence) is given more prominence than the parousia of Christ. This desire is inscribed in the tension between absence and presence to his congregations in his letters, which in turn generates several spectral factors in Paul's assertions of presence, authority, and paternity. Derrida's earlier work on issues of speech vs. writing and presence vs. absence (which continue to be implicit in later works, especially in the variegated performances of iterability), are pertinent to these issues in Paul. What readings could emerge then, if Pauline correspondence is read through a Derridean prism? Does a "Derridean proposal" that, writing "writes itself" out of desire for arrival at a destination yet to come, have value for elucidating an "authority of the text"? This article is a performative engagement with such questions.
LONGINUS AND CAECILIUS: MODELS OF THE SUBLIME
Authors:   Innes
Published: October 2002

The article explores the relationship between Longinus and Caecilius and their range of model specimens. Longinus has a particular interest in Plato, not to defend him but, exploiting his canonical status, to present him as a prime example of the flawed genius. Plato illustrates a style whose rich amplitude carries risks but which proves that sublimity need not always include strong emotion. Caecilius recognised a narrower range of style and his prime model was Demosthenes (Lysias is irrelevant). The article exploits an undervalued source, Tiberius' On Figures in Demosthenes, and argues that there is influence from Caecilius not only in §§43-8, but also in the use of non-Demosthenic examples in §§26-35.
WHY IS THE HOLY IMAGE "TRUE"? THE ONTOLOGICAL CONCEPT OF TRUTH AS A PRINCIPLE OF SELF-AUTHENTICATION OF FOLK DEVOTIONAL EFFIGIES IN THE 18TH AND 19TH CENTURY
Authors: Tokarska-Bakir Joanna
Published: October 2002

The present article examines the twofold material provided by analyses of the borderline between the ethnology of religion and the history of folk art. It refers first of all to the etiological legends of holy images venerated in Central and Eastern Europe in the post-tridentine period, and secondly to folk holy images, in particular woodcut prints, self-declared as "true images," which were widespread until the last century, and richly represented in Polish folk piety.
Despotic societies, sexual attraction and the emergence of male 'tolerance': an agent-based model
Authors: Hemelrijk Charlotte
Published: October 2002

During the period when females are sexually attractive — but only then — males of certain species of primates, such as chimpanzees, allow females access to resources. Because males are usually dominant over females, such male 'tolerance' is explained as a special, reproductive strategy to gain access to females. In this paper a simpler hypothesis is proposed on the basis of an individual-based model (called DomWorld): male 'tolerance' towards females arises in 'despotic' artificial societies as a kind of 'respectful timidity', because sexual attraction automatically increases female dominance over males as a side-effect. The model consists in a homogeneous, virtual world with agents that group and perform dominance-interactions in which the effects of victory and defeat are self-reinforcing. The artificial sexes differ in that VirtualMales have a higher intensity of aggression, they start with a greater capacity to win conflicts than VirtualFemales and they are especially attracted to the opposite sex during certain periods, whereas VirtualFemales are not. I shall explain how the introduction into DomWorld of the attraction of VirtualMales by VirtualFemales leads to female dominance, why it does so only in despotic, but not in egalitarian societies, and how it leads to other phenomena that are relevant to the study of primate behaviour.
Effects of some crop management practices on reproduction of Meloidogyne javanica on Brassica napus
Authors: Steel Christopher , Kirkegaard John , McLeod Rod
Published: October 2002

The effects of seed treatments with pesticides, soil temperature at sowing, cutting of plants with and without glyphosate herbicide, root disruption and age of crop at inoculation on reproduction of Meloidogyne javanica on Brassica napus were investigated. When inoculated at sowing, plants grown from fodder rape cv. Rangi seed treated with fenamiphos (0.35 g a.i. per 100 g) and from fodder swede cv. Highlander seed with a coating including imidacloprid had fewer galls than plants from seed untreated or treated with omethoate (0.7 g a.i. per 100 g). When nematode inoculation was delayed until 4 weeks after sowing, omethoate and the imadacloprid treatments had no effect while fenamiphos (0.7 g a.i. per 100 g seed) suppressed galling but also impaired seedling emergence and induced chlorosis. Green manure rape plants cvs Rangi and Humus transplanted into infested soil in the field in mid-autumn (soil temperature 17°C) remained nematode and gall-free, but tomato cv. Grosse Lisse plants were heavily galled. All three cultivars were gall-free when transplanted and grown in early winter (soil temperatures 8-14°C). Cutting off the tops of cv. Rangi plants at from 6 to 11 weeks after sowing and inoculation had no effect on egg production compared to that on intact plants. Predominant nematode stages in cut plants ranged from developing juveniles to egg-laying females. Application of glyphosate to freshly cut stems had no effect on egg production at any stage. Infesting soil with roots of cv. Rangi, finely chopped while nematodes in them were still juveniles, resulted in a low incidence of infection of bioassay tomato plants compared with infesting soil with rape roots chopped later, when females and females with eggs predominated. Young females in tomato roots laid eggs despite fine chopping of the roots. When cv. Rangi plants were inoculated at 3, 5 and 7 weeks after sowing, the 7-week-old plants were the least invaded and fewer eggs were produced on the 5 and 7-week-old plants than on the 3-week-old ones.
Thrombogenic activity of doxorubicin in myeloma patients receiving thalidomide: implications for therapy
Authors: Zangari Maurizio , Siegel Eric , Barlogie Bart , Anaissie Elias , Saghafifar Fariba , Fassas Athanasios , Morris Christopher , Fink Louis , Tricot Guido
Published: October 2002

Ten percent of newly diagnosed myeloma patients treated with any type of chemotherapy develop deep venous thrombosis (DVT). Thalidomide has proven activity in refractory multiple myeloma (MM), and although single-agent thalidomide has minimal prothrombogenic activity, its combination with cytotoxic chemotherapy is associated with a significantly increased risk of DVT. We analyzed the incidence of DVT in 232 MM patients who received a combination of chemotherapy and thalidomide on 2 protocols that differed only by the inclusion of doxorubicin in one. DT-PACE (dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophos- phanide/etoposide) was offered to patients with preceding standard dose therapy, but no prior autotransplantation, while DCEP-T (dexamethasone/cyclophosphamide/etoposide/cisplatin/thalidomide) was administered for relapse after transplantation. If there were signs or symptoms suggestive of DVT, patients received additional investigations, including Doppler ultrasonography, followed by venography if indicated. Only patients on DT-PACE but not DCEP-T experienced an increased incidence of DVT. A statistical association between the incidence of DVT and combination chemotherapy including doxorubicin (P = .02) was observed; this association was confirmed on multivariate analysis. MM patients treated with thalidomide and doxorubicin have a high risk of developing DVT.
Identification of a novel NCF-1 (p47-phox) pseudogene not containing the signature GT deletion: significance for A47° chronic granulomatous disease carrier detection
Authors: Heyworth Paul G. , Noack Deborah , Cross Andrew R.
Published: October 2002

The p47-phox gene, NCF-1, has 2 nearly identical pseudogenes (ψNCF-1) in proximity at chromosomal locus 7q11.23. A dinucleotide deletion (ΔGT) at the beginning of exon 2 that leads to a frameshift and premature stop codon is considered the signature sequence of the pseudogenes. It is also the most prevalent mutation in p47-phox–deficient (A47°) chronic granulomatous disease (CGD) as a result of the insertion of a ΔGT-containing fragment of pseudogene into NCF-1.Extending our study of the relationship between NCF-1 andψNCF-1 to 53 unaffected control individuals, we found that although in most (n = 44), the ratio of pseudogene (ΔGT) to functional gene (GTGT) sequence in amplicons spanning exon 2 was 2:1, as previously observed, surprisingly, in 7 persons the ratio was 1:1, and in 2 persons the ratio was 1:2. The lowered ratios are explained by the presence, in a heterozygous or homozygous state, respectively, of a pseudogene that contains GTGT rather than ΔGT. It is possible that this pseudogene has not undergone deletion of GT, but more likely, based on analysis of additional NCF-1/ψNCF-1 markers, it represents the previously unidentified product of the reciprocal crossover of DNA fragments between the functional gene and one of its pseudogenes. The mutated NCF-1 resulting from this event is the predominant A47°CGD allele. The existence of 2 extended haplotypes encompassing NCF-1/ψNCF-1 further complicates the detection of A47°CGD carriers. Although most have a ΔGT/GTGT ratio of 5:1, some have a ratio of 2:1 and are indistinguishable by this means from unaffected individuals.
T-cell responses against chronic lymphocytic leukemia cells: implications for immunotherapy
Authors: Krackhardt Angela M. , Harig Sabine , Witzens Mathias , Broderick Ryan , Barrett Patrick , Gribben John G.
Published: October 2002

Chronic lymphocytic leukemia (CLL) cells are ineffective antigen-presenting cells (APCs) although CD40-activated CLL cells can stimulate proliferation of autologous and allogeneic T cells. We examined the antigen-presenting capacity of CD40-activated CLL cells as well as dendritic cells pulsed with apoptotic bodies of CLL cells to generate autologous and allogeneic immune responses against CLL cells. Both APC types were capable of generating T-cell lines that proliferate specifically in response to unstimulated CLL cells. Whereas cytotoxic responses against stimulated and unstimulated CLL cells could be repeatedly generated by allogeneic healthy donors, autologous cytotoxic immune responses against CD40-activated and native CLL cells were rarely detected. However, T cells isolated from patients with CLL could recognize and lyse allogeneic stimulated and unstimulated CLL cells, demonstrating that cytotoxic T cells from these tumor-bearing patients are functionally intact.
Glutathione S-transferase genotypes, genetic susceptibility, and outcome of therapy in childhood acute lymphoblastic leukemia
Authors: Davies Stella M. , Bhatia Smita , Ross Julie A. , Kiffmeyer William R. , Gaynon Paul S. , Radloff Gretchen A. , Robison Leslie L. , Perentesis John P.
Published: October 2002

The glutathione S-transferase (GST) genes are involved in the metabolism of environmental carcinogens and of some classes of chemotherapy drugs. GSTM1 and GSTT1 genotypes are polymorphic in humans, and the phenotypic absence of enzyme activity is caused by a homozygous inherited deletion of the gene. Previous, smaller studies of childhood acute lymphoblastic leukemia (ALL) provided contrasting data on the role of the GST genotype in susceptibility and treatment outcomes. We analyzed GST genotypes in 710 children with ALL treated by the Children's Cancer Group. Frequencies were compared with those of normal controls, and outcomes were analyzed according to genotype. Comparisons of gene frequencies in ALL case and control patients showed similar frequencies (54% vs 53% GSTM1 null in whites,P = .9; 40% versus 32% in blacks,P = .45; 16% versus 15% GSTT1 null in whites,P = .8; 17% versus 28% in blacks,P = .3). ALL was not associated with the GSTM1-null genotype or the double-null genotype in blacks or whites, in contrast to previous reports. Stratification of cases by age at diagnosis, sex, white blood cell count at diagnosis, B or T lineage, or cytogenetics revealed no differences in genotype frequencies. Analysis of treatment outcomes showed no differences in outcome according to GST genotype; in particular, there were no differences in frequencies of relapse at any site. These data, representing a larger series than any reported previously, suggest that GST genotype does not affect etiology or outcome of childhood ALL.
Retroviral transduction of IL2RG into CD34+ cells from X-linked severe combined immunodeficiency patients permits human T- and B-cell development in sheep chimeras
Authors: Tsai Emily J. , Malech Harry L. , Kirby Martha R. , Hsu Amy P. , Seidel Nancy E. , Porada Christopher D. , Zanjani Esmail D. , Bodine David M. , Puck Jennifer M.
Published: October 2002

X-linked severe combined immunodeficiency (XSCID) is caused by mutations of the common gamma chain of cytokine receptors, γc. Because bone marrow transplantation (BMT) for XSCID does not provide complete immune reconstitution for many patients and because of the natural selective advantage conferred on lymphoid progenitors by the expression of normal γc, XSCID is a good candidate disease for therapeutic retroviral gene transfer to hematopoietic stem cells. We studied XSCID patients who have persistent defects in B-cell and/or combined B- and T-cell function despite having received T cell–depleted haploidentical BMT. We compared transduction of autologous B-cell lines and granulocyte colony-stimulating factor–mobilized peripheral CD34+ cells from these patients using an MFGS retrovirus vector containing the γc gene IL2RG pseudotyped with amphotropic, gibbon ape leukemia virus, or RD114 envelopes. Transduced B-cell lines and peripheral CD34+ cells demonstrated provirus integration and new cell-surface γc expression. The chimeric sheep model was exploited to test development of XSCID CD34+ cells into mature myeloid and lymphoid lineages. Transduced and untransduced XSCID CD34+ cells injected into developing sheep fetuses gave rise to myeloid cells. However, only transduced γc+ progenitors from XSCID patients developed into T and B cells. These results suggest that gene transfer to autologous peripheral CD34+ cells using MFGS-gc retrovirus may benefit XSCID patients with persistent T- and B-cell deficits despite prior BMT.
Magnetic resonance imaging of fetal bone marrow for quantitative definition of the human fetal stem cell compartment
Authors: Wilpshaar Jannine , Joekes Elizabeth C. , Lim Frans T. H. , Van Leeuwen Gijs A. M. , Van den Boogaard Pieter J. , Kanhai Humphrey H. H. , Willemze Roel , Falkenburg J. H. Frederik
Published: October 2002

Magnetic resonance imaging (MRI) can be used to distinguish bone marrow (BM) from cartilage and may therefore be used to measure BM volume in intact bones. We used MRI to measure the total human fetal BM volume in intact fetuses during the second trimester of pregnancy and determined the contribution of the individual bones to the total compartment. The total BM volume ranged from 934 μL at 17 to 18 weeks to 4563 μL at 22 to 23 weeks of gestation. The largest contributor to the total BM volume was the spine, constituting 26.4% ± 2.7% of the total volume. By analyzing leukocyte content and percentages of CD34+ cells, lymphocytes, granulocytes, and monocytes of determined volumes, absolute numbers of these cell populations in BM could be measured. The cellular composition of the BM compartment did not significantly change throughout the second trimester of gestation. Absolute white blood cell counts per fetus increased from 111 × 106 at 16 to 17 weeks to 1229 × 106 at 21 to 22 weeks. The absolute numbers of CD34+ cells increased from 25 × 106 at 16 to 17 weeks to 256 × 106 at 21 to 22 weeks. Similar analysis of liver and spleen revealed comparable absolute numbers of CD34+ cells in BM and liver throughout the second trimester of gestation. In fetal liver, CD34+ cells differentiate into red cells, myeloid cells, and platelets, while lymphopoiesis mainly occurs in BM or spleen. Combining MRI and cell counts provides a method to quantify specific cell populations in fetal compartments. This study may enable better evaluation of fetal diagnostics and therapies.
Ectopic expression of TAL-1 protein in Ly-6E.1-htal-1transgenic mice induces defects in B- and T-lymphoid differentiation
Authors: Goardon Nicolas , Schuh Annette , Hajar Iman , Ma Xiaoqian , Jouault Hélène , Dzierzak Elaine , Roméo Paul-Henri , Maouche-Chrétien Leı̈la
Published: October 2002

The tal-1 gene encodes a basic helix-loop-helix (bHLH) transcription factor required for primitive and definitive hematopoiesis. Additionally, ectopic activation of thetal-1 gene during T lymphopoiesis occurs in numerous cases of human T-cell acute lymphoblastic leukemia. With the use of transgenic mice, we show that, in adult hematopoiesis, constitutive expression of TAL-1 protein causes disorders in the hematopoietic lineages that normally switch off tal-1 gene expression during their differentiation process. Myelopoiesis was characterized by a moderate increase of myeloid precursors and by Sca-1 antigen persistence. Although no lymphoid leukemia was observed, T lymphopoiesis and B lymphopoiesis were severely impaired. Transgenic mice showed reduced thymic cellularity together with a decrease in double-positive cells and a concurrent increase in the single-positive population. B cells exhibited a differentiation defect characterized by a reduction of the B-cell compartment most likely because of a differentiation block upstream of the intermediate pro-B progenitor. B cells escaping this defect developed normally, but transgenic splenocytes presented a defect in immunoglobulin class switch recombination. Altogether, these results enlighten the fine-tuning of TAL-1 expression during adult hematopoiesis and indicate why TAL-1 expression has to be switched off in the lymphoid lineages.