bluuebunny/crossref_metadata_2025 huggingface dataset:
Ca2+/calmodulin-dependent protein kinase II inhibition by heparin in mesangial cells
Authors: Xiao Weiqun , Liu Ying , Templeton Douglas M.
Published: September 2004

Heparin exerts an antiproliferative effect in smooth muscle cells, and the Ca2+/calmodulin-dependent protein kinase (CaMK) signaling pathway is heparin sensitive. Here, we report that transfection with a truncated 326-amino acid fragment of CaMK-IIα increases basal activity of CaMK-II in mesangial cells. Ionomycin increased CaMK-II activity in both transfected and untransfected cells, with a concomitant increase in activated Ca2+/calmodulin. Heparin (1 μg/ml), but not chondroitin or dermatan sulfate, significantly attenuated both serum- or ionomycin-induced CaMK-II activity, and attendant c- fos mRNA expression, but did not affect upstream Ca2+/calmodulin. Autophosphorylation of Thr286 generates an autonomously active CaMK-II. Both serum and ionomycin increased phosphorylation at this site and increased CaMK-II activity in antiphosphothreonine immunoprecipitates. Heparin (1 μg/ml) did not inhibit phosphorylation of Thr286 (although much higher concentrations did). Replacement of Thr286 with Asp produces a constitutively active mutant that was insensitive to ionomycin but was inhibited by heparin maximally at 1 μg/ml. These results suggest that heparin at physiological concentrations acts at or downstream of CaMK-II to suppress its activity independent of an effect on autophosphorylation.
A novel pathological role of p53 in kidney development revealed by gene-environment interactions
Authors: Fan Hao , Harrell Jessica R. , Dipp Susana , Saifudeen Zubaida , El-Dahr Samir S.
Published: September 2004

Gene-environment interactions are implicated in congenital human disorders. Accordingly, there is a pressing need to develop animal models of human disease, which are the product of defined gene-environment interactions. Previously, our laboratory demonstrated that gestational salt stress of bradykinin B2receptor (B2R)-null mice induces renal dysgenesis and early death of the offspring (El-Dahr SS, Harrison-Bernard LM, Dipp S, Yosipiv IV, and Meleg-Smith S. Physiol Genomics 3: 121–131, 2000). In contrast, salt-stressed B2R +/+ or +/− littermates have normal development. The present study investigates the mechanisms underlying the susceptibility of B2R-null mice to renal dysgenesis. Proteomic and conventional Western blot screens identified E-cadherin among the differentially repressed proteins in B2R−/− kidneys, whereas the checkpoint kinase Chk1 and its substrate P-Ser20p53 were induced. We tested the hypothesis that p53 mediates repression of E-cadherin gene expression and is causally linked to the renal dysgenesis. Genetic crosses between B2R −/− and p53+/− mice revealed that germline reduction of p53 gene dosage rescues B2R−/− mice from renal dysgenesis and restores kidney E-cadherin gene expression. Furthermore, γ-irradiation induces repression of E-cadherin gene expression in p53+/+ but not −/− cells. In transient transfection assays, p53 repressed human E-cadherin promoter-driven reporter activity, whereas a mutant p53, which cannot bind DNA, did not. Functional promoter analysis indicated the presence of a p53-responsive element in exon 1, which partially mediates p53-induced repression. Chromatin immunoprecipitation assays revealed that p53 inhibits histone acetylation of the E-cadherin promoter. Treatment with a histone deacetylase inhibitor reversed both p53-mediated promoter repression and deacetylation. In conclusion, this study demonstrates that gene-environment interactions cooperate to induce congenital defects through p53 activation.
Excitatory and Inhibitory Postsynaptic Currents in a Rat Model of Epileptogenic Microgyria
Authors: Jacobs K. M. , Prince D. A.
Published: September 2004

Developmental cortical malformations are common in patients with intractable epilepsy; however, mechanisms contributing to this epileptogenesis are currently poorly understood. We previously characterized hyperexcitability in a rat model that mimics the histopathology of human 4-layered microgyria. Here we examined inhibitory and excitatory postsynaptic currents in this model to identify functional alterations that might contribute to epileptogenesis associated with microgyria. We recorded isolated whole cell excitatory postsynaptic currents and GABAA receptor-mediated inhibitory currents (EPSCs and IPSCs) from layer V pyramidal neurons in the region previously shown to be epileptogenic (paramicrogyral area) and in homotopic control cortex. Epileptiform-like activity could be evoked in 60% of paramicrogyral (PMG) cells by local stimulation. The peak conductance of both spontaneous and evoked IPSCs was significantly larger in all PMG cells compared with controls. This difference in amplitude was not present after blockade of ionotropic glutamatergic currents or for miniature (m)IPSCs, suggesting that it was due to the excitatory afferent activity driving inhibitory neurons. This conclusion was supported by the finding that glutamate receptor antagonist application resulted in a significantly greater reduction in spontaneous IPSC frequency in one PMG cell group (PMGE) compared with control cells. The frequency of both spontaneous and miniature EPSCs was significantly greater in all PMG cells, suggesting that pyramidal neurons adjacent to a microgyrus receive more excitatory input than do those in control cortex. These findings suggest that there is an increase in numbers of functional excitatory synapses on both interneurons and pyramidal cells in the PMG cortex perhaps due to hyperinnervation by cortical afferents originally destined for the microgyrus proper.
Task-Specific Sensorimotor Adaptation to Reversing Prisms
Authors: Marotta Jonathan J. , Keith Gerald P. , Crawford J. Douglas
Published: September 2004

We tested between three levels of visuospatial adaptation (global map, parallel feature modules, and parallel sensorimotor transformations) by training subjects to reach and grasp virtual objects viewed through a left-right reversing prism, with either visual location or orientation feedback. Even though spatial information about the global left-right reversal was present in every training session, subjects trained with location feedback reached to the correct location but with the wrong (reversed) grasp orientation. Subjects trained with orientation feedback showed the opposite pattern. These errors were task-specific and not feature-specific; subjects trained to correctly grasp visually reversed–oriented bars failed to show knowledge of the reversal when asked to point to the end locations of these bars. These results show that adaptation to visuospatial distortion—even global reversals—is implemented through learning rules that operate on parallel sensorimotor transformations (e.g., reach vs. grasp).
Angiotensin II type 2 receptor gene transfer elicits cardioprotective effects in an angiotensin II infusion rat model of hypertension
Authors: Falcón Beverly L. , Stewart Jillian M. , Bourassa Erick , Katovich Michael J. , Walter Glenn , Speth Robert C. , Sumners Colin , Raizada Mohan K.
Published: September 2004

The role of the angiotensin II type 2 receptor (AT2R) in cardiovascular physiology remains elusive. We have developed an in vivo lentiviral vector-mediated gene transfer system to study the physiological functions of the AT2R. Our objectives in this study were to determine whether the AT2R influences cardiac hypertrophy and myocardial and perivascular fibrosis in a nongenetic rat model of hypertension. Lentiviral vector containing the AT2R or saline was injected intracardially in 5-day-old Sprague-Dawley rats. This resulted in a persistent overexpression of the AT2R in cardiac tissues. At 15 wk of age, animals were infused with either 200 ng·kg−1·min−1 of angiotensin II or saline by implantation of a 4-wk osmotic minipump. This resulted in an increase in blood pressure (BP) that reached maximal by 2 wk of treatment and was associated with a 123% increase in left ventricular wall thickness (LVWT) and a 129% increase in heart weight to body weight ratios (HW/BW). In addition, the increase in cardiac hypertrophy was associated with a 300% and 158% increase in myocardial and perivascular fibrosis, respectively. Cardiac transduction of the AT2R resulted in an 85% attenuation of LVWT, 91% attenuation of HW/BW, and a 43% decrease in myocardial fibrosis induced by angiotensin infusion. These improvements in cardiac pathology were observed in the absence of attenuation of high BP. Thus our observations indicate that long-term expression of the AT2R in the heart attenuates cardiac hypertrophy and fibrosis in a nongenetic rat model of hypertension.
Cell Adhesion, Polarity, and Epithelia in the Dawn of Metazoans
Authors: Cereijido M. , Contreras R. G. , Shoshani L.
Published: September 2004

Transporting epithelia posed formidable conundrums right from the moment that Du Bois Raymond discovered their asymmetric behavior, a century and a half ago. It took a century and a half to start unraveling the mechanisms of occluding junctions and polarity, but we now face another puzzle: lest its cells died in minutes, the first high metazoa (i.e., higher than a sponge) needed a transporting epithelium, but a transporting epithelium is an incredibly improbable combination of occluding junctions and cell polarity. How could these coincide in the same individual organism and within minutes? We review occluding junctions (tight and septate) as well as the polarized distribution of Na+-K+-ATPase both at the molecular and the cell level. Junctions and polarity depend on hosts of molecular species and cellular processes, which are briefly reviewed whenever they are suspected to have played a role in the dawn of epithelia and metazoan. We come to the conclusion that most of the molecules needed were already present in early protozoan and discuss a few plausible alternatives to solve the riddle described above.
Molecular Structure and Function of the Glycine Receptor Chloride Channel
Authors: Lynch Joseph W.
Published: September 2004

The glycine receptor chloride channel (GlyR) is a member of the nicotinic acetylcholine receptor family of ligand-gated ion channels. Functional receptors of this family comprise five subunits and are important targets for neuroactive drugs. The GlyR is best known for mediating inhibitory neurotransmission in the spinal cord and brain stem, although recent evidence suggests it may also have other physiological roles, including excitatory neurotransmission in embryonic neurons. To date, four α-subunits (α1 to α4) and one β-subunit have been identified. The differential expression of subunits underlies a diversity in GlyR pharmacology. A developmental switch from α2 to α1β is completed by around postnatal day 20 in the rat. The β-subunit is responsible for anchoring GlyRs to the subsynaptic cytoskeleton via the cytoplasmic protein gephyrin. The last few years have seen a surge in interest in these receptors. Consequently, a wealth of information has recently emerged concerning GlyR molecular structure and function. Most of the information has been obtained from homomeric α1 GlyRs, with the roles of the other subunits receiving relatively little attention. Heritable mutations to human GlyR genes give rise to a rare neurological disorder, hyperekplexia (or startle disease). Similar syndromes also occur in other species. A rapidly growing list of compounds has been shown to exert potent modulatory effects on this receptor. Since GlyRs are involved in motor reflex circuits of the spinal cord and provide inhibitory synapses onto pain sensory neurons, these agents may provide lead compounds for the development of muscle relaxant and peripheral analgesic drugs.
Melanin Pigmentation in Mammalian Skin and Its Hormonal Regulation
Authors: Slominski Andrzej , Tobin Desmond J. , Shibahara Shigeki , Wortsman Jacobo
Published: September 2004

Cutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory control by multiple agents interacting via pathways activated by receptor-dependent and -independent mechanisms, in hormonal, auto-, para-, or intracrine fashion. Because of the multidirectional nature and heterogeneous character of the melanogenesis modifying agents, its controlling factors are not organized into simple linear sequences, but they interphase instead in a multidimensional network, with extensive functional overlapping with connections arranged both in series and in parallel. The most important positive regulator of melanogenesis is the MC1 receptor with its ligands melanocortins and ACTH, whereas among the negative regulators agouti protein stands out, determining intensity of melanogenesis and also the type of melanin synthesized. Within the context of the skin as a stress organ, melanogenic activity serves as a unique molecular sensor and transducer of noxious signals and as regulator of local homeostasis. In keeping with these multiple roles, melanogenesis is controlled by a highly structured system, active since early embryogenesis and capable of superselective functional regulation that may reach down to the cellular level represented by single melanocytes. Indeed, the significance of melanogenesis extends beyond the mere assignment of a color trait.
Rigid left Noetherian rings
Authors: Artemovych O. D.
Published: September 2004

We prove thatany rigid left Noetherian ring is either a domain
or isomorphic to some ring of integers modulo
a prime power pn.
Multiple solutions to a nonlinear elliptic equation involving Paneitz type operators
Authors: El Hamidi Abdallah
Published: September 2004

This paper deals with an elliptic equation involving Paneitz
type operators on compact Riemannian manifolds with
concave‐convex nonlinearities and a real parameter. Nonlocal
and multiple existence results are established.
Characteristic values of the real parameter are introduced
and their role in the change of the energy sign and the
existence of positive solutions are highlighted.
Unit 1‐stable range for ideals
Authors: Chen Huanyin , Chen Miaosen
Published: September 2004

We investigate necessary and sufficient conditions
under which a ring satisfies unit 1‐stable range
for an ideal. As an application, we prove that R

satisfies unit 1‐stable range for I if and only
if QM2(R) satisfies unit 1‐stable range for
QM2(I).
On the stabilization of internally coupled map lattice systems
Authors: Huang Weihong
Published: September 2004

The adaptive adjustment mechanism is applied to the stabilization
of an internally coupled map lattice system defined by
xi,t+1 = G((1 − αi − βi)xi,t + αixi+1,t + βixi−1,t),
where f : ℝ → ℝ is a
nonlinear map, and α and β are nonnegative coupling
constants that satisfy the constraint
αi + βi < 1, for all x ∈ ℝ, i = 1, 2, …, n. Sufficient conditions and ranges of adjustment
parameters that guarantee the local stability of a generic steady
state have been provided. Numerical simulations have demonstrated
the effectiveness and efficiency for this mechanism to stabilize
the system to a generic unstable steady state or a periodic orbit.
Periodic solutions and stability for a delayed discrete ratio‐dependent predator‐prey system with Holling‐type functional response
Authors: Wang Lin-Lin , Li Wan-Tong
Published: September 2004

The existence of positive periodic solutions for a delayed
discrete predator‐prey model with Holling‐type‐III functional
response , is established by using the coincidence
degree theory. We also present sufficient conditions for the
globally asymptotical stability of this system when all the delays
are zero. Our investigation gives an affirmative exemplum for the
claim that the ratio‐dependent predator‐prey theory is more
reasonable than the traditional prey‐dependent predator‐prey
theory.
Quadratic regular reversal maps
Authors: Solis Francisco J. , Jódar Lucas
Published: September 2004

We study families of quadratic maps in an attempt to understand
the role of dependence on parameters of unimodal maps and its
relationship with the computer‐generated chaos observed in
numerical simulations. Our specific goal is to give conditions on
this dependence to avoid chaotic situations. We show several
examples that describe in some generality the qualitative
properties of quadratic maps.
Summaries of certain spatial patterns retrieved from multidate remote‐sensing data
Authors: Nair Hema
Published: September 2004

This paper presents an approach to describe patterns in
remote‐sensed images utilising fuzzy logic. The truth of a
linguistic proposition such as Y is F can be determined for
each pattern characterised by a tuple in the database, where Y is
the pattern and F is a summary that applies to that pattern.
This proposition is formulated in terms of primary quantitative
measures, such as area, length, perimeter, and so forth, of the
pattern. Fuzzy descriptions of linguistic summaries help to
evaluate the degree to which a summary describes a pattern or
object in the database. Techniques, such as clustering and genetic
algorithms, are used to mine images. Image mining is a relatively
new area of research. It is used to extract patterns from
multidated satellite images of a geographic area.
On well‐posedness of the nonlocal boundary value problem for parabolic difference equations
Authors: Ashyralyev A. , Karatay I. , Sobolevskii P. E.
Published: September 2004

We consider the nonlocal boundary value problem for difference
equations (uk − uk−1)/τ + Auk = φk, 1 ≤ k ≤ N, Nτ = 1, and u0 = u[λ/τ] + φ, 0 < λ ≤ 1, in an
arbitrary Banach space E with the strongly positive operator
A. The well‐posedness of this nonlocal boundary value problem
for difference equations in various Banach spaces is studied. In
applications, the stability and coercive stability estimates in
Hölder norms for the solutions of the difference
scheme of the mixed‐type boundary value problems for the
parabolic equations are obtained. Some results of numerical
experiments are given.
Fast Measurement of Left Ventricular Mass With Real-Time Three-Dimensional Echocardiography
Authors: Mor-Avi Victor , Sugeng Lissa , Weinert Lynn , MacEneaney Peter , Caiani Enrico G. , Koch Rick , Salgo Ivan S. , Lang Roberto M.
Published: September 2004

Background—

Left ventricular (LV) mass is an important predictor of morbidity and mortality, especially in patients with systemic hypertension. However, the accuracy of 2D echocardiographic LV mass measurements is limited because acquiring anatomically correct apical views is often difficult. We tested the hypothesis that LV mass could be measured more accurately from real-time 3D (RT3D) data sets, which allow offline selection of nonforeshortened apical views, by comparing 2D and RT3D measurements against cardiac MR (CMR) measurements.

Methods and Results—

Echocardiographic imaging was performed (Philips 7500) in 21 patients referred for CMR imaging (1.5 T, GE). Apical 2- and 4-chamber views and RT3D data sets were acquired and analyzed by 2 independent observers. The RT3D data sets were used to select nonforeshortened apical 2- and 4-chamber views (3DQ-QLAB, Philips). In both 2D and RT3D images, LV long axis was measured; endocardial and epicardial boundaries were traced, and mass was calculated by use of the biplane method of disks. CMR LV mass values were obtained through standard techniques (MASS Analysis, GE). The RT3D data resulted in significantly larger LV long-axis dimensions and measurements of LV mass that correlated with CMR better (
r
=0.90) than 2D (
r
=0.79). The 2D technique underestimated LV mass (bias, 39%), whereas RT3D measurements showed only minimal bias (3%). The 95% limits of agreement were significantly wider for 2D (52%) than RT3D (28%). Additionally, the RT3D technique reduced the interobserver variability (37% to 7%) and intraobserver variability (19% to 8%).

Conclusions—

RT3D imaging provides the basis for accurate and reliable measurement of LV mass.
Prognostic Impact of Plasma N-Terminal Pro–Brain Natriuretic Peptide in Severe Chronic Congestive Heart Failure
Authors: Hartmann Franz , Packer Milton , Coats Andrew J.S. , Fowler Michael B. , Krum Henry , Mohacsi Paul , Rouleau Jean L. , Tendera Michal , Castaigne Alain , Anker Stefan D. , Amann-Zalan Ildiko , Hoersch Silke , Katus Hugo A.
Published: September 2004

Background—

The utility of N-terminal proBNP (NT-proBNP) to predict the occurrence of death and hospitalization was prospectively evaluated in the COPERNICUS study, which enrolled patients with an ejection fraction <25% and symptoms of chronic congestive heart failure at rest or on minimal exertion.

Methods and Results—

Baseline plasma concentrations of NT-proBNP were measured in a subgroup of 814 men and 197 women with symptoms at rest or on minimal exertion who were enrolled in the COPERNICUS study and were randomized to placebo (n=506) or carvedilol (n=505). Values of NT-proBNP were markedly increased despite the requirement that patients be euvolemic before the start of treatment (mean±SD, 3235±4392 pg/mL; median, 1767 pg/mL). By univariate Cox regression analysis, NT-proBNP was found to be a powerful predictor of subsequent all-cause mortality (relative risk [RR], 2.7; 95% CI, 1.7 to 4.3;
P
=0.0001 for above versus below median) and all-cause mortality or hospitalization for heart failure (RR, 2.4; 95% CI, 1.8 to 3.4;
P
=0.0001 for above versus below median). The predictive value of NT-proBNP was similar when both placebo and carvedilol patients were analyzed separately. No significant interaction was found between NT-proBNP and treatment group (
P
=0.93 for above- versus below-median NT-proBNP).

Conclusions—

NT-proBNP was consistently associated with increased risk for all-cause mortality and for all-cause mortality or hospitalization for heart failure in patients with severe congestive heart failure, even in those who were clinically euvolemic. This marker therefore may be a useful tool in risk stratification of patients with severe congestive heart failure.
Insights Into Causal Pathways for Ischemic Heart Disease
Authors: Dong Maxia , Giles Wayne H. , Felitti Vincent J. , Dube Shanta R. , Williams Janice E. , Chapman Daniel P. , Anda Robert F.
Published: September 2004

Background—

The purpose of this study was to assess the relation of adverse childhood experiences (ACEs), including abuse, neglect, and household dysfunction, to the risk of ischemic heart disease (IHD) and to examine the mediating impact on this relation of both traditional IHD risk factors and psychological factors that are associated with ACEs.

Methods and Results—

Retrospective cohort survey data were collected from 17 337 adult health plan members from 1995 to 1997. Logistic regression adjusted for age, sex, race, and education was used to estimate the strength of the ACE–IHD relation and the mediating impact of IHD risk factors in this relation. Nine of 10 categories of ACEs significantly increased the risk of IHD by 1.3- to 1.7-fold versus persons with no ACEs. The adjusted odds ratios for IHD among persons with ≥7 ACEs was 3.6 (95% CI, 2.4 to 5.3). The ACE–IHD relation was mediated more strongly by individual psychological risk factors commonly associated with ACEs than by traditional IHD risk factors. We observed significant association between increased likelihood of reported IHD (adjusted ORs) and depressed affect (2.1, 1.9 to 2.4) and anger (2.5, 2.1 to 3.0) as well as traditional risk factors (smoking, physical inactivity, obesity, diabetes and hypertension), with ORs ranging from 1.2 to 2.7.

Conclusions—

We found a dose-response relation of ACEs to IHD and a relation between almost all individual ACEs and IHD. Psychological factors appear to be more important than traditional risk factors in mediating the relation of ACEs to the risk of IHD. These findings provide further insights into the potential pathways by which stressful childhood experiences may increase the risk of IHD in adulthood.
Health System Costs of Out-of-Hospital Cardiac Arrest in Relation to Time to Shock
Authors: van Alem Anouk P. , Dijkgraaf Marcel G.W. , Tijssen Jan G.P. , Koster Rudolph W.
Published: September 2004

Background—

Early defibrillation results in higher admission rates and healthcare costs. This study determined the healthcare resources used and related medical costs after out-of-hospital cardiac arrest (OHCA) in relation to time to shock. We assessed the incremental healthcare costs per life gained from reduction in time to shock of 2, 4, and 6 minutes.

Methods and Results—

Clinical and costs data of patients in witnessed OHCA with ventricular fibrillation as initial rhythm were collected. Each patient’s time to shock was estimated and assigned to 1 of 3 categories: ≤7 minutes (early), 7 to 12 minutes (intermediate), and >12 minutes (late). Incremental cost-effectiveness analysis and Monte Carlo simulation compared scenarios of reduction in time to shock of 2, 4, and 6 minutes. Six-month survival was 22%. Mean prehospital, in-hospital, and posthospital costs in the first half-year after OHCA were €559, €6869 and €666. Mean costs were €28 636 per survivor and €2384 per nonsurvivor. Among patients shocked early (n=24), 46% survived, with costs averaging €20 253. Of the intermediate group (n=149), 26% survived, with costs averaging €31 467. Among patients shocked late (n=135), 13% survived, with costs averaging €27 781. The point estimates of the incremental cost-effectiveness ratios of reduction of time to shock of 2, 4, and 6 minutes compared with baseline were €17 508, €14 303, and €12 708 per life saved, respectively.

Conclusions—

Costs per survivor were lowest with the shortest time to shock because of shorter stay in the intensive care unit. Reducing the time to defibrillation increases the healthcare costs by an acceptable amount according to current standards and is economically attractive.
Expression of Vascular Endothelial Growth Factor Receptor-2 or Tie-2 on Peripheral Blood Cells Defines Functionally Competent Cell Populations Capable of Reendothelialization
Authors: Nowak Grzegorz , Karrar Azza , Holmén Carolina , Nava Silvia , Uzunel Mehmet , Hultenby Kjell , Sumitran-Holgersson Suchitra
Published: September 2004

Background—

Receptor tyrosine kinases that include vascular endothelial growth factor (VEGFR)-1, VEGFR-2, and Tie-2 regulate cardiovascular development and physiological and pathological angiogenesis. We were interested in the phenotypic and functional characterization of peripheral blood cells expressing these receptors and their therapeutic potential in vascular injury.

Methods and Results—

VEGFR-1
+
, VEGFR-2
+
, and Tie-2
+
cells constituted ≈3.0±0.2%, 0.8±0.5%, and 2.0±0.3%, respectively, of the total population of mononuclear cells in blood. Phenotypic analysis demonstrated that all 3 cell populations mainly expressed markers of monocytic/macrophage lineage. Only VEGFR-2
+
and Tie-2
+
cells phenotypically, morphologically, and functionally differentiated to endothelial cells after culture, whereas VEGFR-1
+
cells did not. None of the cell types proliferated in vitro. Only freshly isolated VEGFR-2
+
or Tie-2
+
cells but not VEGFR-2
−
or Tie-2
−
cell populations significantly contributed to efficient endothelialization of balloon-injured femoral arteries of nude mice. Furthermore, these cells also differentiated into α-actin–positive smooth muscle cells. Administration of bromodeoxyuridine to animals transplanted with human endothelial progenitor cells showed that VEGFR-2
+
and Tie-2
+
cells proliferated in vivo.

Conclusions—

These data demonstrate that expression of VEGFR-2 and/or Tie-2 on peripheral blood cells defines functionally competent cell populations that proliferate in vivo and that contribute to reendothelialization. These findings may have implications for a cell-based approach in vascular diseases.
Clinical Outcomes in the Diabetes Cohort of the International Verapamil SR-Trandolapril Study
Authors: Bakris George L. , Gaxiola Efrain , Messerli Franz H. , Mancia Giuseppe , Erdine Serap , Cooper-DeHoff Rhonda , Pepine Carl J.
Published: September 2004

The INternational VErapamil SR-Trandolapril study (INVEST) had 6400 of 22 576 (28.3%) participants with diabetes at entry. The objectives of this prespecified analysis were to compare antihypertensive treatment strategies in the diabetes cohort (verapamil SR-based [n=3169] versus atenolol-based [n=3231]) and identify predictors for the primary outcome (a composite of first occurrence of all-cause death, nonfatal myocardial infarction, or nonfatal stroke). During a mean follow-up of 2.7 years, 913 participants with diabetes experienced a primary outcome event, with no significant difference between treatment strategies (14.6%, verapamil SR versus 13.9%; atenolol hazard ratio, 1.05; 95% confidence interval, 0.92 to 1.19). Risk for the primary outcome increased with presence of baseline heart failure, renal impairment, US residency, age, previous stroke/transient ischemic attack, previous myocardial infarction, peripheral vascular disease, or smoking. High systolic and diastolic pressures during follow-up also were associated with increased risk, as were low diastolic pressures. Antihypertensive treatment with a verapamil SR or atenolol strategy resulted in similar rates of cardiovascular outcomes in coronary artery disease (CAD) patients with diabetes. Thus, a verapamil SR-based antihypertensive treatment strategy is an alternative to a β-blocker–based strategy in adults with CAD and diabetes.
NO Synthase Inhibition Increases Aldosterone in Humans
Authors: Muldowney James A.S. , Davis Stephen N. , Vaughan Douglas E. , Brown Nancy J.
Published: September 2004

To test the hypothesis that NO influences aldosterone production in humans, we examined the effect of
N
G
-nitro-
l
-arginine methyl ester (
l
-NAME) on aldosterone concentrations in the presence and absence of the NO precursor
l
-arginine (3 g TID) and the angiotensin-converting enzyme inhibitor ramipril (10 mg QD). Ten normal subjects were given
l
-NAME (66 μg/kg per min for 30 minutes) or vehicle in random order on separate days during placebo and after randomized, double-blind treatment with
l
-arginine, ramipril, or
l
-arginine plus ramipril. Infusion of
l
-NAME significantly increased systolic blood pressure (all
P
<0.05) and decreased heart rate (all
P
≤0.02) during all 4 treatment arms. After placebo pretreatment, serum aldosterone was significantly higher during
l
-NAME infusion than during vehicle (6.6±1.7 versus 3.3±0.5 ng/dL;
P
=0.045). Combined treatment with
l
-arginine plus ramipril abolished this effect. There was no effect of
l
-NAME on plasma renin activity (PRA;
P
=0.297) or angiotensin II concentrations (
P
=0.537). However, there was a significant interactive effect of
l
-NAME and time on serum potassium (
P
=0.039). There was a significant linear relationship between PRA and aldosterone concentration after vehicle infusion ([aldosterone]=3.9·PRA+1.9;
r
2
=0.476;
P
=0.027) and
l
-NAME infusion ([aldosterone]=7.2·PRA+3.1;
r
2
=0.457;
P
=0.032), and the intercepts of these lines were different (
P
=0.029). There was a significant linear relationship between serum potassium and aldosterone during
l
-NAME ([aldosterone]=8.2 · [potassium]−28.9;
r
2
=0.609;
P
=0.008) but not during vehicle (
P
=0.313). These data suggest that endogenous NO modulates aldosterone synthesis in humans.
Sustained Sympathoinhibitory Effects of Cardiac Resynchronization Therapy in Severe Heart Failure
Authors: Grassi Guido , Vincenti Antonio , Brambilla Roberta , Trevano Fosca Quarti , Dell’Oro Raffaella , Cirò Antonio , Trocino Giuseppe , Vincenzi Antonella , Mancia Giuseppe
Published: September 2004

Evidence is available that in heart failure, cardiac resynchronization therapy by biventricular pacing improves myocardial function and exercise capacity. Whether this is accompanied by a sustained inhibition of heart failure–dependent sympathoexcitation is uncertain. In 11 heart failure patients (mean±SEM age, 68.4±1.5 years) in New York Heart Association (NYHA) class III and IV under medical treatment with an intraventricular conduction delay (QRS duration ≥130 ms), with a markedly depressed left ventricular ejection fraction, and undergoing implantation of a biventricular pacemaker, we measured beat-to-beat blood pressure and muscle sympathetic nerve traffic. Measurements, which also included echocardiographic and clinical variables, were performed before and ≈10 weeks after successful resynchronization therapy. Ten age- and NYHA class–matched heart failure patients who were under medical treatment for the same time period served as controls. Long-term resynchronization therapy improved cardiac function and caused a significant increase in systolic blood pressure coupled with an improvement in maximal oxygen consumption and exercise capacity. These effects were coupled with a significant and marked reduction in sympathetic nerve traffic when expressed both as burst frequency over time (44.1±3.6 vs 30.7±3.0 bs/min, −30.5%,
P
<0.02) and as burst frequency corrected for heart rate (68.3±5.9 vs 47.3±4.3 bs/100 beats, −32.1%,
P
<0.02). No significant change in the aforementioned parameters was seen in the control group. These data provide the first direct evidence that in severe heart failure, resynchronization therapy exerts a marked and sustained sympathoinhibition. Because in heart failure sympathetic overactivity adversely affects prognosis, this may have important clinical implications.
Rosetta Stone? Hockney, Falco and the Sources of “Opticality” in Lorenzo Lotto's Husband and Wife
Authors: Tyler Christopher
Published: September 2004

In his book Secret Knowledge, David Hockney proposes that the “optical quality” of Flemish art arose around 1420, because artists such as van Eyck then began to use optical devices for accurate projection of subject images onto the canvas. Although Hockney describes Lotto's Man and Wife as the “Rosetta Stone” of his argument, the author's analysis reveals that its perspective structure is incompatible with the logic of local optical projection. Regions that should be geometrically coherent in an optical projection display pronounced distortions, while regions that should be incoherent show no such distortions. Such detailed evidence, as well as the inability of optical projection to capture the effect of windblown garments, is inconsistent with Hockney's claim.
Wave Space Art
Authors: Peden Douglas D.
Published: September 2004

The author presents the basics of his painting style and the development of its underlying geometry, which he calls GridField Geometry.
Kid Friendly, Open Source
Authors: Wallace Linda
Published: September 2004

A dispatch on the arts, technologies and cultures in the metropolitan community served by the Amsterdam airport.
Before Timur Came: Provincialization of the Delhi Sultanate Through The Fourteenth Century
Authors: Digby Simon
Published: September 2004

The present essay examines information on the relationship of provincial settlements in the territories of the Dehli Sultanate with the capital city during the fourteenth century. This is drawn mainly from hagiographical sources in Persian rather than the much-utilized series of chronicles compiled in the city of Dehli itself. After a brief discussion of some of the factors of continuity and change operative in the fourteenth century in the territories of the Dehli Sultanate, it turns to a series of case studies, where evidence is available, of the processes of settlement of Muslim communities under the aegis of the Sultans of Dehli and in a radius extending from the capital city in northern India. The main routes of extension were to the south and to the east. Evidence suggests a process of growth of provincial centers of power to the detriment of the authority of the Sultan and the administration lodged in the capital city before the collapse of this authority in 1398. The latter part of the paper examines the linguistic consequences of the provincial political developments of the fourteenth century. It is argued that these affected changes in North Indian climates of sensibility that have endured to the present day. L'article étudie les informations sur la relation entre les établissement régionaux dans les territoires du Sultanat de Dehli et la ville capitale durant le XIV e siècle. Ces données sont surtout puisées aux sources hagiographiques en langue persane plutôt qu'aux séries de chroniques compilées dans la ville de Dehli elle-même. Après une discussion concise de certains facteurs responsables de la continuité et du changement en vigueur au XIVe siècle dans les territoires du Sultantat de Dehli, un nombre d'études de cas passe la revue — en fonction des temoignages disponibles. Elles traitent les processus d'établissement des communautés musulmanes sous la protection des sultans de Dehli et dans un rayon autour de la ville capitale de l'Inde septentrionale. Les principales routes d'épanouissment menèrent du Sud vers l'Est. Les temoignages suggèrent une croissance des centres de pouvoir régionaux au détriment de l'autorité du Sultan et son administration, logées dans la ville capitale jusqu'à son écroulement en 1398. La dernière section de l'article étudie les conséquences linguistiques des développements politiques et régionaux du XIV e siècle. Il est avancé que ces changements engendrèrent des modi fications dans les climats de sensibilité dans l'Inde septentrionale qui ont duré jusqu'à nos jours.
The Deccan Frontier and Mughal Expansion, Ca. 1600: Contemporary Perspectives
Authors: Subrahmanyam Sanjay , Alam Muzaffar
Published: September 2004

This essay explores the situation in the Deccan in the late sixteenth and early seventeenth centuries, at a time when the Mughal empire was expanding over the Ahmadnagar Sultanate and beginning to threaten both Bijapur and Goa. It does so through a close reading of two sources, the reports of the Mughal court-poet Abu'l Faiz 'Faizi,' who was sent there as a Mughal envoy in the early 1590s; and the autobiographical text of Asad Beg Qazwini, who followed Faizi some ten years later. It seeks to demonstrate the role of the Deccan as frontier zone in this period, not only between northern and southern India, but equally between Safavid Iran and Mughal India. Cet essai est consacré à l'étude de la situation politique dans le Deccan au tournant du XVIIe siècle, en s'appuyant sur deux sources peu explorées. La première est la collection des rap- ports envoyés par le poète et diplomate Abu'l Faiz 'Faizi', qui se trouvait dans le Deccan autour de 1591-92 comme représentant de l'empereur moghol Akbar. La seconde source est le récit autobiographique d'Asad Beg Qazwini, également envoyé par les Moghols au début du XVIIe siècle dans une mission auprès du Sultan de Bijapur, Ibrahim II. Nous nous efforçons de démontrer le rôle du Deccan comme région frontière, à la fois entre l'Inde du Nord et l'Inde du Sud, et entre les zones d'in fluences des Moghols et des Safavides.
Ancient Mesopotamian House Gods
Authors: Scurlock Joann
Published: September 2004

The gods of the Mesopotamian house appear to have been Gula, Ištar, Išum, and the Pleiades, as well as toilet demon 'Šulak, the gate-guarding Kusarikku, and the divine protectors of other, lesser, parts of the house.
"Ich Spreche Ständig Zu Aton...": Zur Menschgott-beziehung in Der Amarna Religion
Authors: Bickel Susanne
Published: September 2004

Very little is known about the impact of the Amarna revolution on individual religious feeling and belief. This article gathers various traces of individual religiosity at Amarna. Traditional divine forces (Toeris, Bes, Hathor), and the king, but also the god Aten could be addressed as guarantors of health and prosperity. Several sources show that individuals of varying social status could have knowledge of and direct contact with Aten, despite the assertion in the Great Hymn that these were exclusively royal privileges. The expression of individual religiosity was possible within the context of Amarna religion in forms that continue earlier ways of approaching the divine and prefigure Ramesside modes of expression of personal piety.
Zum Hethitischen Schutzgott Der Lanze
Authors: Popko Maciej
Published: September 2004

Der Schutzgott der Lanze ist in den Keilschrifttexten aus Bo Å azköy ab mittelhethitischer Zeit belegt. Dieser Gott südlicher, vielleicht luwischer Herkunft wurde vor allem von den Angehörigen der königlichen Leibgarde, ferner auch von den "Leuten der Lanze" verehrt, deswegen befand sich sein Altar im "Hof der Leibgarde" in der Burg von ] attu à a. Die Lanze wird gelegentlich als Symbol des Gottes betrachtet, aber Beweise für die Richtigkeit dieser Auffassung fehlen. Die Begriffe "der Schutzgott der Lanze" und "die Lanze des/eines Schutzgottes" sind nicht zu verwechseln.
Creencias y actitudes hacia la inmigración: estereotipos, prejuicio y regulaciones normativas
Authors: Valencia José-Francisco , Gil-De-Montes Lorena , Elejabarrieta Francisco
Published: September 2004

Se analizan las relaciones entre creencias y actitudes, así como diferentes regulaciones normativas en la explicación de los estereotipos y prejuicio hacia los inmigrantes. En los dos estudios las medidas de respuesta libre sobre creencias aportan una apreciable consistencia en su relación con las actitudes. Igualmente se encuentra una evaluación más positiva de los emigrantes en la condición normativa individual que en la normativa de sustitución. El segundo estudio plantea las diferencias de evaluación entre los grupos de inmigrantes argentinos y magrebíes. Finalmente, se defiende la pertinencia de la teoría de las Representaciones Sociales para explicar las diferentes lógicas que el metasistema induce en la actuación en las operaciones cognitivas.
Semejanzas y diferencias de género en las actitudes hacia las demandas del mercado laboral
Authors: González José-Ma , Zarco Victoria
Published: September 2004

A pesar de las acciones desarrolladas durante los últimos años en el terreno legal, político, económico y cultural para favorecer la equidad y la paridad de género, es probable que en el ámbito psicosocial aún persistan ciertas diferencias psicológicas y actitudinales entre hombres y mujeres que, por su propio carácter implícito e informal, resultan poco visibles y difíciles de detectar pero sobre las que, sin duda, merece la pena investigar. Con esta intención, presentamos este trabajo en el que se analizan, a través de un cuestionario de elaboración propia, las semejanzas y diferencias de género existentes en una muestra de 438 jóvenes universitarios en relación con las actitudes hacia las actuales demandas del mercado laboral. Los resultados obtenidos son interpretados a la luz de los tres principales modelos teóricos desarrollados en este campo (modelo del género, modelo del trabajo y modelo integrado) y nos muestran cómo hombres y mujeres coinciden en las valoraciones que realizan sobre dichos requerimientos, atribuyen a las mismas razones la imposición en el mundo laboral de estas demandas y, finalmente, también convergen en las características profesionales que desearían, y por tanto, elegirían si se les diera tal oportunidad.
Conflictos matrimoniales y problemas en los hijos
Authors: Ramírez María-Aurelia
Published: September 2004

La investigación que presentamos estudia la validez ecológica de la educación familiar. Con este propósito se examina el efecto de los conflictos matrimoniales en el desarrollo de los hijos. El estudio se realiza con una muestra de 200 sujetos con un amplio rango de edad. Los resultados obtenidos corroboran estudios previos (Cumming, 1994; Cumming y Davies, 1994; Neighbors, Forenhand y Bau, 1997) y muestran la relación entre conflictos matrimoniales y problemas de conducta en los hijos. Concretamente se confirma que los hijos que presencian conflictos matrimoniales continuados tienen gran probabilidad de presentar problemas sobre todo de externalización. Además, se demuestra el papel modulador del género y de la edad.
Angiostatin is a novel anti-inflammatory factor by inhibiting leukocyte recruitment
Authors: Chavakis Triantafyllos , Athanasopoulos Athanasios , Rhee Joong-Sup , Orlova Valeria , Schmidt-Wöll Thomas , Bierhaus Angelika , May Andreas E. , Celik Ilhan , Nawroth Peter P. , Preissner Klaus T.
Published: September 2004

Angiogenesis and inflammation are closely related biologic processes in wound healing and the responses to vascular injury as well as in cardiovascular diseases; however, the molecular connections are poorly defined. In particular, it is yet unclear whether endogenous factors can regulate both angiogenesis and inflammation. Here, we show that the endogenous angiogenesis inhibitor, angiostatin (containing kringle domains 1-4 of plasminogen), serves an anti-inflammatory role, since the kringles 1-3 and its kringle 4 directly interact with leukocyte β1- and β2-integrins, respectively. In particular, a specific interaction between kringle 4 and αMβ2-integrin (Mac-1) but not leukocyte function antigen 1 (LFA-1) was identified. Angiostatin thereby inhibited β1- and β2-integrin–mediated adhesion of leukocytes to extracellular matrix proteins and the endothelium as well as their transmigration through the endothelium in vitro. Moreover, angiostatin blocked the peritonitis-induced neutrophil emigration in vivo. In addition, through its interaction with Mac-1, angiostatin reduced activation of the proinflammatory transcription factor nuclear factor κB (NFκB), as well as the NFκB-related expression of tissue factor, a potent initiator of hemostasis following vascular injury. Finally, angiostatin forms were generated in vivo following skin injury/inflammation and were detectable during the following entire period of wound healing peaking at the terminal phase of the healing process. Taken together, over and above inhibition of neovascularization, angiostatin was identified as an antiadhesive/anti-inflammatory substance. These observations could provide the basis for new therapeutic applications of angiostatin to target chronic inflammatory processes in different pathologic situations.
Wiskott-Aldrich syndrome protein deficiency leads to reduced B-cell adhesion, migration, and homing, and a delayed humoral immune response
Authors: Westerberg Lisa , Larsson Malin , Hardy Samantha J. , Fernández Carmen , Thrasher Adrian J. , Severinson Eva
Published: September 2004

The Wiskott-Aldrich syndrome protein (WASp) is mutated in the severe immunodeficiency disease Wiskott-Aldrich syndrome (WAS). The function of B cells and the physiologic alterations in WAS remain unclear. We show that B cells from WAS patients exhibited decreased motility and had reduced capacity to migrate, adhere homotypically, and form long protrusions after in vitro culture. WASp-deficient murine B cells also migrated less well to chemokines. Upon antigen challenge, WASp-deficient mice mounted a reduced and delayed humoral immune response to both T-cell–dependent and –independent antigens. This was at least in part due to deficient migration and homing of B cells. In addition, the germinal center reaction was reduced in WASp-deficient mice. Thus, WASp is crucial for optimal B-cell responses and plays a pivotal role in the primary humoral immune response.