bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequence Elements in both the Intergenic Space and the 3′ Untranslated Region of the
Crithidia fasciculata KAP3
Gene Are Required for Cell Cycle Regulation of
KAP3
mRNA
Authors: Avliyakulov Nuraly K. , Hines Jane C. , Ray Dan S.
Published: August 2003

mRNA levels of several
Crithidia fasciculata
genes involved in DNA metabolism have previously been found to cycle as cells progress through the cell cycle. Octamer consensus sequences in the 5′ untranslated regions (5′ UTRs) of these transcripts were shown to be required for cycling of these mRNAs. The
KAP3
gene encodes a kinetoplast histone H1-like DNA binding protein, and its mRNA levels cycle in parallel with those of the kinetoplast DNA topoisomerase (TOP2), dihydrofolate reductase-thymidylate synthase (DHFR-TS), and the large subunit of the nuclear single-stranded DNA binding protein (RPA1).
KAP3
mRNA contains two octamer consensus sequences in its 3′ UTR but none in its 5′ UTR. Mutation of these octamer sequences was not sufficient to prevent cycling of a sequence-tagged
KAP3
mRNA expressed from a plasmid. Mutation of an octamer sequence contained on the precursor transcript but not on the mRNA, in addition to mutation of the two octamer sequences in the 3′ UTR, was necessary to abolish cycling of the mRNA. The requirement for a sequence not present on the mature mRNA indicates that regulation of the mRNA levels by the octamer sequences occurs at or prior to splicing of the transcript. Incompletely processed RNAs containing octamer sequences were also found to accumulate during the cell cycle when the mRNA levels were lowest. These RNA species hybridize to both the
KAP3
coding sequence and that of the downstream drug resistance gene, indicating a lack of processing within the intergenic region separating these genes. We propose a cell cycle-dependent interference in transcript processing mediated by octamer consensus sequences as a mechanism contributing to the cycling of such transcripts.
Environmental Suppression of
Neurospora crassa cot-1
Hyperbranching: a Link between COT1 Kinase and Stress Sensing
Authors: Gorovits Rena , Yarden Oded
Published: August 2003

cot-1
mutants belong to a class of
Neurospora crassa
colonial temperature-sensitive (
cot
) mutants that exhibit abnormal polar extension and branching patterns when grown at restrictive temperatures.
cot-1
encodes a Ser/Thr protein kinase that is structurally related to the human myotonic dystrophy kinase which, when impaired, confers a disease that involves changes in cytoarchitecture and ion homeostasis. When grown under restrictive conditions,
cot-1
cultures exhibited enhanced medium acidification rates, increased relative abundance of sodium, and increased intracellular glycerol content, indicating an ion homeostasis defect in a hyperbranching mutant. The application of ion transport blockers led to only mild suppression of the
cot-1
phenotype. The presence of increased medium NaCl or sorbitol, H
2
O
2
, or ethanol levels significantly suppressed the
cot-1
phenotype, restored ion homeostasis, and was accompanied by reduced levels of cyclic AMP-dependent protein kinase (PKA) activity. The
cot-1
phenotype could also be partially suppressed by direct inhibition of PKA with KT-5720. A reduced availability of fermentable carbon sources also had a suppressive effect on the
cot-1
phenotype. In contrast to the effect of extragenic
ropy
suppressors of
cot-1
, environmental stress-related suppression of
cot-1
did not change COT1 polypeptide expression patterns in the mutant. We suggest that COT1 function is linked to environmental stress response signaling and that altering PKA activity bypasses the requirement for fully functional COT1.
Protein Kinase Involved in Flagellar-Length Control
Authors: Wiese Martin , Kuhn Daniela , Grünfelder Christoph G.
Published: August 2003

During its life cycle, the parasitic protozoon
Leishmania mexicana
differentiates from a flagellated form, the promastigote, to an amastigote form carrying a rudimentary flagellum. Besides biochemical changes, this process involves a change in overall cell morphology including flagellar shortening. A mitogen-activated protein kinase kinase homologue designated LmxMKK was identified in a homology screening and found to be critically involved in the regulation of flagellar assembly and cell size. LmxMKK is exclusively expressed in the promastigote stage and is likely to be regulated by posttranslational mechanisms such as phosphorylation. A deletion mutant for the single-copy gene revealed motile flagella dramatically reduced in length and lacking the paraflagellar rod, a structure adjacent to the axoneme in kinetoplastid flagella. Moreover, a fraction of the cells showed perturbance of the axonemal structure. Complementation of the deletion mutant with the wild-type gene restored typical promastigote morphology. We propose that LmxMKK influences anterograde intraflagellar transport to maintain flagellar length in
Leishmania
promastigotes; as such, it is the first protein kinase known to be involved in organellar assembly.
Formation of Hirano Bodies Induced by Expression of an Actin Cross-Linking Protein with a Gain-of-Function Mutation
Authors: Maselli Andrew , Furukawa Ruth , Thomson Susanne A. M. , Davis Richard C. , Fechheimer Marcus
Published: August 2003

Hirano bodies are paracrystalline actin filament-containing structures reported to be associated with a variety of neurodegenerative diseases. However, the biological function of Hirano bodies remains poorly understood, since nearly all prior studies of these structures were done with postmortem samples of tissue. In the present study, we generated a full-length form of a
Dictyostelium
34-kDa actin cross-linking protein with point mutations in the first putative EF hand, termed 34-kDa ΔEF1. The 34-kDa ΔEF1 protein binds calcium normally but has activated actin binding that is unregulated by calcium. The expression of the 34-kDa ΔEF1 protein in
Dictyostelium
induces the formation of Hirano bodies, as assessed by both fluorescence microscopy and transmission electron microscopy.
Dictyostelium
cells bearing Hirano bodies grow normally, indicating that Hirano bodies are not associated with cell death and are not deleterious to cell growth. Moreover, the expression of the 34-kDa ΔEF1 protein rescues the phenotypes of cells lacking the 34-kDa protein and cells lacking both the 34-kDa protein and α-actinin. Finally, the expression of the 34-kDa ΔEF1 protein also initiates the formation of Hirano bodies in cultured mouse fibroblasts. These results show that the failure to regulate the activity and/or affinity of an actin cross-linking protein can provide a signal for the formation of Hirano bodies. More generally, the formation of Hirano bodies is a cellular response to or a consequence of aberrant function of the actin cytoskeleton.
Specific Protein Targeting during Cell Differentiation: Polarized Localization of Fus1p during Mating Depends on Chs5p in
Saccharomyces cerevisiae
Authors: Santos Beatriz , Snyder Michael
Published: August 2003

In budding yeast,
chs5
mutants are defective in chitin synthesis and cell fusion during mating. Chs5p is a late-Golgi protein required for the polarized transport of the chitin synthase Chs3p to the membrane. Here we show that Chs5p is also essential for the polarized targeting of Fus1p, but not of other cell fusion proteins, to the membrane during mating.
The Homotopy Type of the Symmetric Products of Bouquets of Circles
Authors: Ong Boon W.
Published: August 2003

A wedge of k circles is homotopy equivalent to the plane with k points removed. By looking at [Formula: see text]∖{w1, …, wk} instead of ⋁k S1, we could view the symmetric product of a wedge of k circles as [Formula: see text], the complement space [3] of a hyperplane arrangement, [Formula: see text]. Applying a theorem of Hattori [2], we see that if k > n, the symmetric product of ⋁k S1 is, up to homotopy, the union of n-dimensional subtorii in a k-torus.
Representation Rings of Classical Groups and Hopf Algebras
Authors: Zhou Jian
Published: August 2003

We prove a double coset formula for induced representations of compact Lie groups. We apply it to the representation rings of unitary and symplectic groups to obtain Hopf algebras. We also construct a Heisenberg algebra representation based on the restiction and induction of representations of unitary groups.
A Polynomial-Time Algorithm for Computing Shortest Paths of Bounded Curvature Amidst Moderate Obstacles
Authors: Boissonnat Jean-Daniel , Lazard Sylvain
Published: August 2003

In this paper, we consider the problem of computing shortest paths of bounded curvature amidst obstacles in the plane. More precisely, given two prescribed initial and final configurations (specifying the location and the direction of travel) and a set of obstacles in the plane, we want to compute a shortest C1 path joining those two configurations, avoiding the obstacles, and with the further constraint that, on each C2 piece, the radius of curvature is at least 1. In this paper, we consider the case of moderate obstacles and present a polynomial-time exact algorithm to solve this problem.
Infimaximal Frames: A Technique for Making Lines Look Like Segments
Authors: Mehlhorn Kurt , Seel Michael
Published: August 2003

Many geometric algorithms that are usually formulated for points and segments generalize easily to inputs also containing rays and lines. The sweep algorithm for segment intersection is a prototypical example. Implementations of such algorithms do, in general, not extend easily. For example, segment endpoints cause events in sweep line algorithms, but lines have no endpoints. We describe a general technique, which we call infimaximal frames, for extending implementations to inputs also containing rays and lines. The technique can also be used to extend implementations of planar subdivisions to subdivisions with many unbounded faces. We have used the technique successfully in generalizing a sweep algorithm designed for segments to rays and lines and also in an implementation of planar Nef polyhedra.14,1

Our implementation is based on concepts of generic programming in C++ and the geometric data types provided by the C++ Computational Geometry Algorithms Library (CGAL).
QCD and Rescattering in Nuclear Targets
Authors: Qiu Jianwei , Sterman George
Published: August 2003

We review the extension of the factorization formalism of perturbative QCD to soft rescattering associated with hard processes in nuclei.
Decomposition of Ge2H6 on the Si(100)(2 × 1) Surface
Authors: Katırcıoğlu Şenay
Published: August 2003

The decomposition of Ge 2 H 6 on Si(100)(2 × 1) was investigated on different adsorption models of fragments using the density functional theory method. The most probable adsorption models of fragments for low and high surface coverage of Ge 2 H 6 have been obtained by geometry optimization and single value relative energy calculations. It has been found that, Ge 2 H 4 makes a bridge between the adjacent surface dimers, Ge 2 H 5–H is bound to the same dimer bond with an unbroken Ge–Ge bond in Ge 2 H 6, and two GeH 3 sticks to the same surface dimer bond by a broken Ge–Ge bond in Ge 2 H 6. The parallel dimer bond structure of Si(100) was conserved in these models after geometry optimization.
A Theoretical Study of a H–H Pair on the BCC Fe(100) Surface
Authors: Gonzalez E. , Brizuela G. , Pistonesi C. , Juan A.
Published: August 2003

Hydrogen adsorption on Fe(100) was analyzed using a semiempirical theoretical method. Calculations were performed using a Fe 130 cluster. Adsorption sites for one and two hydrogen atoms on the surface correspond to local energy minima configurations.

Changes in the electronic structure of surface Fe atoms were analyzed for the system without hydrogen and with one and two adsorbed hydrogen atoms. Fe atoms close to H weaken their metallic bond. This is due to the formation of H–Fe bonds. Hydrogen influences only its nearest neighbor Fe atoms. The H–H interaction was also analyzed and our results show that H–Fe interaction is much stronger than any possible H–H interaction. No additional decohesion is observed in the Fe–Fe bonds; however, more Fe–Fe bonds are affected.
S Adsorption at Regular and Defect Sites of the MgO (001) Surface: Cluster Model Study at DFT Level
Authors: Xu Yi-Jun , Li Jun-Qian , Zhang Yong-Fan
Published: August 2003

We have studied the adsorption of sulfur at regular and defect sites of the MgO (001) surface using cluster models embedded in a large array of point charges by the density functional method. The calculated results indicate that it is a chemical adsorption regarding sulfur at both the regular site and the defect site of the MgO (001) surface. Especially for sulfur adsorbed at different oxygen vacancy sites (F, F + and F 2+ centers) and different magnesium vacancy sites (V, V - and V 2- centers), it has very large adsorption energies, which reflects the fact that the MgO (001) surface with the vacancies is an excellent adsorbent for sulfur adsorption. Besides, we find that the adsorbed sulfur is almost inserted into the lattice for sulfur adsorbed at the magnesium vacancy site of the MgO (001) surface. The adsorption energy of sulfur on the MgO (001) surface with magnesium vacancies is much larger when compared to that on the MgO (001) surface with oxygen vacancies. At the same time, it is also found that the S behaves as an electron acceptor except that it is adsorbed at the magnesium vacancy site behaving as an electron donor.
Heteroepitaxial System of h-BN/Monolayer Graphene on Ni(111)
Authors: Tanaka T. , Itoh A. , Yamashita K. , Rokuta E. , Oshima C.
Published: August 2003

A heteroepitaxial system of h-BN/monolayer graphene on Ni(111) has been investigated by means of vibrational spectroscopy, accompanied by low energy electron diffraction (LEED) and Auger electron spectroscopy (AES). The system was prepared in an epitaxial manner on a Ni(111) surface by chemical vapor deposition (CVD). We found that phonon peaks in observed spectra showed typical features of Fuchs–Kliewer (FK) phonons. The vibrational spectra of h-BN films ranging in thickness from 0 to 8.7 monolayers have been compared with theoretical spectra based on a dielectric theory. Detailed analysis has revealed new types of phonons, of which the vibrational amplitudes are localized at edges of h-BN nanocrystals. In addition, we have observed subsidence phenomena of the graphene and h-BN layers into Ni substrate at elevated temperatures.
Growth of a New Ternary BON Crystal on Si(100) by Plasma-Assisted MOCVD and Study on the Effects of Fed Gas and Growth Temperature
Authors: Chen G. C. , Lee S.-B. , Boo J.-H.
Published: August 2003

A new ternary BO x N y crystal was grown on Si(100) substrate at 500°C by low-frequency (100 kHz) radio-frequency (rf) derived plasma-assisted MOCVD with an organoborate precursor. The as-grown deposits were characterized by SEM, TED, XPS, XRD, AFM and FT-IR. The experimental results showed that BO x N y crystal was apt to be formed at N-rich atmosphere and high temperature. The decrease of hydrogen flux in fed gases was of benefit to form BON crystal structure. The crystal structure of BO x N y was as similar to that of H 3 BO 3 in this study.
Study of Improvement Technology of Photocatalytic Activity on the TiO2 Sol by Plasma Treatment After Dip-Coating Processing
Authors: Jung C.-K. , Cho S.-H. , Lee S.-B. , Kim T.-K. , Lee M.-N. , Boo J.-H.
Published: August 2003

We have deposited titanium dioxide TiO 2 thin films on glass using a single molecular precursor such as titanium (IV) isopropoxide ( Ti [ OCH ( CH 3)2]4, 97%) by sol–gel processing. Argon and oxygen rf plasma treatments at 295 K for 0.5 h in the power range of 50–200 W were also used to elevate photocatalytic activity of the as-grown TiO 2 films. A superhydrophilic property and surface morphology change appeared in the light irradiation with O 2 plasma treatment. In this work, the effect of the plasma with photocatalyst ( TiO 2) on the improvement of hydrophilic properties has mainly been investigated. Photocatalytic activity was evaluated by measurements of the uv/vis. irradiation, refractive index, contact angle, and AFM analysis. We confirmed that plasma treatment is a very reliable method for the synthesis of TiO 2 thin films with high catalytic performance.
Finite Element Analysis of Optical Bistability in One-Dimensional Nonlinear Photonic Band Gap Structures with a Defect
Authors: Suryanto A. , van Groesen E. , Hammer M.
Published: August 2003

We present a new approach based on the recently reported finite element scheme16 to study the optical response of a finite one-dimensional nonlinear grating. Using the transmitted wave amplitude as a numerical input parameter, we are able to find all stable and unstable solutions related to a specific incident wave which build up the complete bistability curve. The method is applied to investigate the optical bistability in a nonlinear quarter-wave reflector with a defect. With a proper choice of the incident light frequency, a very low bistability threshold is predicted for an optimized defect structure.
Optical Pulse Deformation in Second Order Nonlinear Media
Authors: van Groesen E.
Published: August 2003

The deformation of optical pulses in one dimensional lossless second order nonlinear media is considered. Using a KdV-type of equation, with dispersion determined by the material properties, the deformation of a bichromatic initial signal is studied. An explicit expression for a third order approximation is used and the maximal temporal amplitude MTA is investigated. This MTA is obtained by looking at the maximum over time of the amplitude at each position. It is shown that modulations of the carrier waves and of the envelopes of the bound and free third order terms determine respectively the oscillations and the recurrence of the MTA curve. We will illustrate the explicit formula with numerical displays for the characteristic cases.
Options with Multiple Reset Rights
Authors: Dai Min , Kwok Yue Kuen , Wu Li Xin
Published: August 2003

The reset right embedded in a derivative refers to the feature that the holder can alter certain terms in the derivative contract according to some preset rules. In this paper, we consider options that allow the holder to reset the strike price with preset number of times at any moment during the life of the option. The determination of the optimal reset policies adopted by the holder leads to a free boundary value problem. We explore how the critical asset value at which the holder should exercise the reset right optimally depends on the number of reset rights remaining, the relative magnitude of the riskless interest rate and dividend yield, the original strike price set at initiation, etc. In particular, we examine the asymptotic behaviors of the optimal reset policies at infinite time to expiry and the existence of threshold time earlier than which the holder should never shout.
Jump Diffusion Models for Risky Debts: Quality Spread Differentials
Authors: Wong Hoi Ying , Kwok Yue Kuen
Published: August 2003

The quality spread differential is defined to be the difference between the default premiums demanded for fixed rate and floating rate risky debts. The risky debt model based on Merton's firm value approach is used to examine the behaviors of the quality spread differential of fixed rate and floating rate debts. We extend earlier result by adopting Geometric Brownian diffusion process with jumps for the underlying firm value process of the debt issuer. Closed form formulas are obtained for the default premiums for risky debts. The impact of the jumps on the fixed-floating spread differential is examined.
Ethanol Inhibits Fibroblast Growth Factor–Induced Proliferation of Aortic Smooth Muscle Cells
Authors: Ghiselli Giancarlo , Chen Jia , Kaou Mohamad , Hallak Hazam , Rubin Raphael
Published: August 2003

Objective—

Epidemiological studies have demonstrated that moderate alcohol consumption reduces mortality associated with coronary artery disease. The protective effect is correlated with the amount of ethanol consumed but is unrelated to the form of alcoholic beverage. Adoption of a favorable lipoprotein profile accounts for about half of the protective action of alcohol, but the remaining causative factors remain conjectural. Fibroblast growth factors (FGFs) play important roles in mediating smooth muscle cell (SMC) proliferation and migration, which are key factors in the atherosclerotic process. In the present study, we examined the effect of ethanol on FGF-mediated SMC growth and signaling.

Methods and Results—

Pharmacologically relevant concentrations of ethanol inhibited the proliferation of a rat aortic SMC line (SV40LT-SMCs) in response to FGF1 and FGF2. Human aortic SMC growth was similarly inhibited by ethanol. Transition into the G
2
/M phase was specifically affected. FGF-mediated phosphorylation of p42/p44 mitogen-activated protein kinase (MAPK) c-Raf, MAP kinase kinase kinase, MEK1/2 MAP kinase, kinase, stress-activated protein kinase/c-Jun–NH
2
-terminal kinase, and p38 MAPK were variably reduced by ethanol. The inhibition of intracellular signaling by ethanol was correlated with inhibition of FGF receptor autophosphorylation. By contrast, neither epidermal growth factor receptor autophosphorylation nor epidermal growth factor–mediated p42/p44 MAPK activation was affected by ethanol.

Conclusions—

The findings identify the FGF receptor as an inhibitory target for ethanol, which could account in part for the inhibitory actions of ethanol on SMC proliferation observed in vivo.
Cisapride-Induced Transmural Dispersion of Repolarization and Torsade de Pointes in the Canine Left Ventricular Wedge Preparation During Epicardial Stimulation
Authors: Di Diego José M. , Belardinelli Luiz , Antzelevitch Charles
Published: August 2003

Background—

Cisapride, a gastrointestinal prokinetic agent, was recently withdrawn from the market because of its propensity to induce torsade de pointes (TdP) arrhythmias. The present study examines the electrophysiological actions of cisapride in the isolated arterially perfused canine left ventricular wedge preparation.

Methods and Results—

Transmembrane action potentials from epicardial and M regions and a pseudo-ECG were simultaneously recorded. Cisapride (0.1 to 5 μmol/L) was added to the coronary perfusate. Cisapride prolonged the QT interval and increased transmural dispersion of repolarization (TDR) at relatively low but not at high concentrations. TdP could be induced with programmed electrical stimulation only at a low concentration of drug (0.2 μmol/L), when TDR was maximally prolonged. Moreover, TdP could only be induced during epicardial (but not endocardial) activation of the wedge, which was found to augment TDR. At higher concentrations of cisapride, QT was further prolonged, TDR was diminished, and TdP could no longer be induced. T
peak
–T
end
interval and T
peak
–T
end
area provided reasonable electrocardiographic indices of TDR.

Conclusion—

Our data (1) demonstrate a biphasic concentration/response relationship for the effect of cisapride to induce long-QT syndrome and TdP, (2) show the value of the left ventricular wedge preparation in identifying drugs that pose an arrhythmic risk, (3) support the hypothesis that risk for development of TdP is related to the increase in TDR rather than to prolongation of the QT interval, and (4) indicate that epicardial activation of the left ventricle, as occurs during biventricular pacing, can facilitate the development of TdP under long-QT conditions.
Relation Between Hospital Intra-Aortic Balloon Counterpulsation Volume and Mortality in Acute Myocardial Infarction Complicated by Cardiogenic Shock
Authors: Chen Edmond W. , Canto John G. , Parsons Lori S. , Peterson Eric D. , Littrell Katherine A. , Every Nathan R. , Gibson C. Michael , Hochman Judith S. , Ohman E. Magnus , Cheeks Morris , Barron Hal V.
Published: August 2003

Background—

Increasing evidence suggests an inverse relationship between outcome and the total number of invasive cardiac procedures performed at a given hospital. The purpose of the present study was to determine if a similar relationship exists between the number of intra-aortic balloon counterpulsation (IABP) procedures performed at a given hospital per year and the in-hospital mortality rate of patients with acute myocardial infarction complicated by cardiogenic shock.

Methods and Results—

We analyzed data of 12 730 patients at 750 hospitals enrolled in the National Registry of Myocardial Infarction 2 from 1994 to 1998. The hospitals were divided into tertiles (low–, intermediate–, and high–IABP volume hospitals) according to the number of IABPs performed at the given hospital per year. The median number of IABPs performed per hospital per year was 3.4, 12.7, and 37.4 IABPs at low-, intermediate-, and high-volume hospitals, respectively. Of those patients who underwent IABP, there were only minor differences in baseline patient characteristics between the 3 groups. Crude mortality rate decreased with increasing IABP volume: 65.4%, lowest volume tertile; 54.1%, intermediate volume tertile; and 50.6%, highest volume tertile (
P
for trend <0.001). This mortality difference represented 150 fewer deaths per 1000 patients treated at the high IABP hospitals. In the multivariate analysis, high hospital IABP volume for patients with acute myocardial infarction was associated with lower mortality (OR=0.71, 95% CI=0.56 to 0.90), independent of baseline patient characteristics, hospital factors, treatment, and procedures such as PTCA.

Conclusions—

Among the myocardial infarction patients with cardiogenic shock who underwent IABP placement, mortality rate was significantly lower at high–IABP volume hospitals compared with low–IABP volume hospitals.
Natural History of Asymptomatic Left Ventricular Systolic Dysfunction in the Community
Authors: Wang Thomas J. , Evans Jane C. , Benjamin Emelia J. , Levy Daniel , LeRoy Elizabeth C. , Vasan Ramachandran S.
Published: August 2003

Background—

Information is limited regarding the rates of progression to congestive heart failure (CHF) and death in individuals with asymptomatic left ventricular systolic dysfunction (ALVD). We sought to characterize the natural history of ALVD, by studying unselected individuals with this condition in the community.

Methods and Results—

We studied 4257 participants (1860 men) from the Framingham Study who underwent routine echocardiography. The prevalence of ALVD (visually estimated ejection fraction [EF]≤50% without a history of CHF) was 6.0% in men and 0.8% in women. During up to 12 years of follow-up, rates of CHF among subjects with normal left ventricular systolic function (EF >50%, n=4128) and ALVD (n=129) were 0.7 and 5.8 per 100 person-years, respectively. After adjustment for cardiovascular disease risk factors, ALVD was associated with a hazards ratio (HR) for CHF of 4.7 (95% CI 2.7 to 8.1), compared with individuals without ALVD. An elevated risk of CHF after ALVD was observed even in individuals without prior myocardial infarction or valvular disease, with an adjusted HR of 6.5 (CI 3.1 to 13.5). Mild ALVD (EF 40% to 50%, n=78) and moderate-to-severe ALVD (EF <40%, n=51) were associated with adjusted HRs for CHF of 3.3 (CI 1.7 to 6.6) and 7.8 (CI 3.9 to 15.6), respectively. ALVD was also associated with an increased mortality risk (adjusted HR 1.6, CI 1.1 to 2.4). The median survival of ALVD subjects was 7.1 years.

Conclusion—

Individuals with ALVD in the community are at high risk of CHF and death, even when only mild impairment of EF is present. Additional studies are needed to define optimal therapy for mild ALVD.
Seasonal Variation of Fibrinogen in Dipper and Nondipper Hypertensive Patients
Authors: Hermida Ramón C. , Calvo Carlos , Ayala Diana E. , López José E. , Fernández José R. , Mojón Artemio , Domínguez María J. , Covelo Manuel
Published: August 2003

Background—

A seasonal variation with higher values in winter has been previously reported in plasma fibrinogen, a recognized marker of the potential risk of myocardial infarction and stroke. The lack of nocturnal decline in blood pressure has also been associated with an increase in cardiovascular events. Accordingly, we have compared the yearly variation of plasma fibrinogen in dipper and nondipper hypertensive patients.

Methods and Results—

We studied 1006 stage 1 to 2 hypertensive patients (482 men and 524 women, 53.0±13.4 years of age). Blood pressure was measured every 20 minutes during the day and every 30 minutes at night for 48 consecutive hours. Physical activity was simultaneously evaluated at 1-minute intervals with a wrist actigraph. A blood sample was collected on the same day before starting blood pressure monitoring. The circannual variation of fibrinogen was established for all patients as well as for subgroups of dippers and nondippers (n=513; nocturnal blood pressure decline <10%) by multiple-component analysis. For the whole group of patients, fibrinogen was characterized by a highly significant seasonal variation (
P
<0.001) with a mean value of 318 mg/dL, double circannual amplitude (extent of predictable change along the year) of 40 mg/dL, and time of peak value in February. Throughout the year, the nondippers showed higher plasma fibrinogen levels than did the dippers (
P
<0.001).

Conclusions—

The elevated plasma fibrinogen levels in nondipper patients appear to be directly related to their increased risk in vascular events, which are more prominent during the late winter months.
Antioxidant Vitamins C and E Improve Endothelial Function in Children With Hyperlipidemia
Authors: Engler Marguerite M. , Engler Mary B. , Malloy Mary J. , Chiu Elisa Y. , Schloetter Monique C. , Paul Steven M. , Stuehlinger Markus , Lin Ken Y. , Cooke John P. , Morrow Jason D. , Ridker Paul M , Rifai Nader , Miller Elizabeth , Witztum Joseph L. , Mietus-Snyder Michele
Published: August 2003

Background—

Hyperlipidemia is associated with endothelial dysfunction, an early event in atherosclerosis and predictor of risk for future coronary artery disease. Epidemiological studies suggest that increased dietary intake of antioxidants reduces the risk of coronary artery disease. The purpose of this study was to determine whether antioxidant vitamin therapy improves endothelial function and affects surrogate biomarkers for oxidative stress and inflammation in hyperlipidemic children.

Methods and Results—

In a randomized, double-blind, placebo-controlled trial, the effects of antioxidant vitamins C (500 mg/d) and E (400 IU/d) for 6 weeks and the National Cholesterol Education Program Step II (NCEP-II) diet for 6 months on endothelium-dependent flow-mediated dilation (FMD) of the brachial artery were examined in 15 children with familial hypercholesterolemia (FH) or the phenotype of familial combined hyperlipidemia (FCH). Antioxidant vitamin therapy improved FMD of the brachial artery compared with baseline (
P
<0.001) without an effect on biomarkers for oxidative stress (autoantibodies to epitopes of oxidized LDL, F
2
-isoprostanes, 8-hydroxy-2′-deoxyguanosine), inflammation (C-reactive protein), or levels of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide.

Conclusions—

Antioxidant therapy with vitamins C and E restores endothelial function in hyperlipidemic children. Early detection and treatment of endothelial dysfunction in high-risk children may retard the progression of atherosclerosis.
Role of a Decreased Expression of the Local Renin-Angiotensin System in the Etiology of Cerebral Aneurysms
Authors: Ohkuma Hiroki , Suzuki Shigeharu , Fujita Seiichiroh , Nakamura Wataru
Published: August 2003

Background—

Local renin-angiotensin systems (RAS) have been implicated as playing an important role in vascular remodeling. The relationship of this system to the etiology of cerebral aneurysm was investigated.

Methods and Results—

The aneurysmal wall from patients with a ruptured or unruptured cerebral aneurysm and the cortical cerebral artery in control patients with head trauma or a glioma were taken during surgery for study. Local RAS were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and/or immunohistochemistry. RT-PCR analysis revealed a significantly decreased expression of angiotensin-converting enzyme (ACE), angiotensin type 1 (AT
1
) receptor, basic fibroblast growth factor, platelet-derived growth factor-AA, and tissue inhibitor of matrix metalloproteinases-1 mRNA in the aneurysmal wall as compared with the control cortical arterial wall. Immunohistochemistry also revealed a decreased expression of ACE, AT
1
receptor, and angiotensin II in the aneurysmal wall.

Conclusion—

Expression of local RAS was decreased in the aneurysmal wall, which may induce aneurysm formation caused by a lack of vascular remodeling that prevents the arterial wall from thickening under increased hemodynamic stress. This is the first report that suggests that a decreased expression of local RAS plays a part in the pathogenesis of any disease.
Soluble CD40L
Authors: Varo Nerea , de Lemos James A. , Libby Peter , Morrow David A. , Murphy Sabina A. , Nuzzo Rebecca , Gibson C. Michael , Cannon Christopher P. , Braunwald Eugene , Schönbeck Uwe
Published: August 2003

Background—

Elevated plasma concentrations of soluble CD40 ligand (sCD40L) indicate increased risk for future cardiovascular events in apparently healthy women. This study tested the hypothesis that plasma sCD40L, alone or in combination with troponin (cTnI) or C-reactive protein (CRP), may identify patients with acute coronary syndromes at heightened risk for recurrent cardiac events.

Methods and Results—

In a nested case-control study (cases, n=195; controls, n=195) within the OPUS-TIMI16 trial, patients with the prespecified study end points death, myocardial infarction (MI), or congestive heart failure (CHF) within 10 months had significantly higher median (25th, 75th percentiles) sCD40L plasma levels than did controls (0.78 [0.34, 1.73] ng/mL versus 0.52 [0.16, 1.42] ng/mL,
P
<0.002). After adjustment for other risk predictors and levels of cTnI and CRP, sCD40L levels above median were associated with higher risk for death, MI, and the composite death/MI or death/MI/CHF (adjusted hazard ratios, 1.9 [
P
<0.05], 1.9 [
P
<0.001], 1.9 [
P
<0.001], and 1.8 [
P
<0.01], respectively). Interestingly, patients with elevated plasma levels of sCD40L and cTnI showed a markedly increased risk of death, MI, or death/MI/CHF compared with patients with the lowest levels of both markers (adjusted hazard ratios, 12.1, 7.2, and 4.3, respectively; all
P
<0.01).

Conclusions—

Elevated plasma levels of sCD40L identify patients with acute coronary syndromes at heightened risk of death and recurrent MI independent of other predictive variables, including cTnI and CRP. Notably, combined assessment of sCD40L with cTnI complements prognostic information for death and MI.
Training-Induced, Pressure-Lowering Effect in SHR
Authors: Melo Ronaldo Meira , Martinho Eduardo , Michelini Lisete Compagno
Published: August 2003

We showed that the training-induced, pressure-lowering effect correlates with decreased arteriole wall/lumen ratio and venule growth in the gracilis muscle. To investigate whether these beneficial changes are tissue-specific or occur in other muscles and tissues, we analyzed the effects of hypertension and training on microcirculatory profile of locomotor/nonlocomotor muscles and another nonmuscular tissue. Spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats were submitted to low-intensity training (50% to 60% maximal exercise capacity, 13 weeks); age-matched control rats were kept sedentary. Trained and sedentary rats were instrumented for pressure and heart rate measurements at rest. Morphometric analyses (arterioles, capillaries, venules) were performed in all tissues. Training attenuated pressure and heart rate only in SHR. Arterioles (inner diameter <30 μm) were markedly hypertrophied in sedentary SHR, but wall/lumen ratio was equally reduced (≈30%) and normalized by training in locomotor (soleus, gastrocnemius, gracilis) and nonlocomotor skeletal muscles (temporalis) in the myocardium and diaphragm, without changes in the renal cortex. Training also increased venule density (≈2-fold) only in locomotor and nonlocomotor muscles of SHR. Capillary density was similarly increased in all exercised muscles of both groups, with no change in temporalis and kidneys. Data suggest that growth/proliferation of small venules and regression of hypertrophied arteriole wall/lumen ratio are generalized tissue-specific (skeletal muscle) and group-specific (SHR) adjustments to training to reduce local resistance and augment physical capacity of circulation, thus contributing to training-induced pressure-lowering effect. They are accompanied by remodeling of myocardium (cardiac output) and diaphragm arterioles (ventilatory adjustments), stressing the importance of training as a nonpharmacological therapy to control pressure levels in hypertension.
Chronic Salt Loading Upregulates Expression of Adrenomedullin and Its Receptors in Adrenal Glands and Kidneys of the Rat
Authors: Cao Yuan-Ning , Kitamura Kazuo , Kato Johji , Kuwasako Kenji , Ito Kaoru , Onitsuka Hisamitsu , Nagoshi Yasuko , Uemura Tomohiko , Kita Toshihiro , Eto Tanenao
Published: August 2003

The vasodilator peptide adrenomedullin (AM) elicits diuresis and natriuresis and inhibits aldosterone secretion. The aim of this study was to better understand the role of AM in maintaining water and electrolyte balance during chronic salt loading. Male Wistar rats were divided into a high salt (HS) group that received a diet containing 8% sodium chloride (NaCl) and a normal salt group that received a diet containing 0.4% NaCl. Plasma AM concentrations as well as expression of AM mRNA in the adrenal gland and kidney were then measured after 3, 7, 14, and 28 days. After 28 days, sodium and water excretion were significantly higher in HS rats than in control, although blood pressure and fluid volume were not significantly affected. Moreover, although plasma AM remained unchanged for up to 14 days, it was increased 2.5-fold in HS rats after 28 days on a high salt diet, and there were corresponding 3-fold and 1.5-fold increases in the levels of AM mRNA in the adrenal gland and kidney, respectively. At the same time, expression of calcitonin receptor-like receptor mRNA was significantly upregulated in both kidney and adrenal gland, as was expression of receptor activity-modify protein 1 (RAMP1) and RAMP2 mRNA in the adrenals and expression of RAMP3 in kidneys. Taken together, these results suggest that AM plays a role in the regulation of water and electrolyte balance in animals chronically ingesting high levels of salt.
Endothelial and Platelet Activation in Acute Ischemic Stroke and Its Etiological Subtypes
Authors: Cherian Paul , Hankey Graeme J. , Eikelboom John W. , Thom Jim , Baker Ross I. , McQuillan Andrew , Staton Janelle , Yi Qilong
Published: August 2003

Background and Purpose—

Activation of endothelial cells and platelets is an important mediator of atherothrombosis. Markers of endothelial cell and platelet activation such as soluble adhesion molecules can be measured in plasma. We hypothesized that patients with acute ischemic stroke would have increased blood concentrations of soluble E-selectin and von Willebrand factor (vWF), primarily reflecting activation of endothelial cells, and increased concentrations of soluble P-selectin and platelet-derived microvesicles (PDM), primarily reflecting activation of platelets, compared with healthy controls. We also hypothesized that these markers would be differentially elevated in ischemic stroke caused by large- and small-artery atherothrombosis compared with cardiogenic embolism.

Methods—

We conducted a case-control study of 200 hospital-referred cases of first-ever ischemic stroke and 205 randomly selected community controls stratified by age, sex, and postal code. Using established criteria, we classified cases of stroke by etiological subtype in a blinded fashion. The prevalence of vascular risk factors and blood concentrations of E-selectin, P-selectin, vWF antigen, and PDM were determined in stroke cases within 7 days and at 3 to 6 months after stroke and in controls.

Results—

Mean blood concentrations of soluble E-selectin, P-selectin, and PDM within 7 days of stroke onset were all significantly higher in cases compared with controls. At 3 to 6 months after stroke, the mean blood concentrations of E-selectin and P-selectin fell significantly below that of controls, and PDM concentrations remained elevated. There was a strong, graded, and independent (of age, sex, and vascular risk factors) association between increasing blood concentrations of E-selectin during the acute phase and all etiological subtypes of ischemic stroke, particularly ischemic stroke caused by large-artery atherothrombosis. There was also a significant, graded, and independent association between increasing blood concentrations of vWF during the acute phase and ischemic stroke caused by large-artery atherothrombosis.

Conclusions—

We have demonstrated significant associations between acute elevation of blood markers of endothelial cell and platelet activation and ischemic stroke and between acute elevation of blood markers of endothelial cell activation and ischemic stroke caused by large-artery atherothrombosis. Persistent elevated blood concentrations of PDM may be a marker of increased risk of ischemic stroke.
Impact of Hospital-Related Factors on Outcome After Treatment of Cerebral Aneurysms
Authors: Berman Mitchell F. , Solomon Robert A. , Mayer Stephan A. , Johnston S. Claiborne , Yung Pixie P.
Published: August 2003

Background and Purpose—

The goal of this study was to examine the impact of hospital characteristics on outcome after the treatment of ruptured and unruptured cerebral aneurysms.

Methods—

We identified all discharges in New York State from 1995 through 2000 with a principal diagnosis of subarachnoid hemorrhage (SAH) or unruptured cerebral aneurysm (UCA) in patients who were treated by aneurysm clipping, wrapping, or endovascular coiling. An adverse outcome was defined as in-hospital death or discharge to a rehabilitation hospital or long-term facility. We examined the effect of hospital factors, including the rate of endovascular therapy and overall procedural volume, on outcome, length of stay, and total charges.

Results—

There were 2200 (36.9%) and 3763 (63.1%) admissions for attempted treatment of UCA and SAH, respectively. The 10 highest-volume hospitals performed half of all the procedures. Overall, hospital volume was associated with fewer adverse outcomes and lower in-hospital mortality for both UCA (adverse outcome: odds ratio [OR], 0.89;
P
<0.0001; mortality: OR, 0.94;
P
=0.002 for each 10 additional procedures performed per year) and SAH (adverse outcome: OR, 0.94;
P
=0.03; mortality: OR, 0.95;
P
=0.005). Use of endovascular therapy (each additional 10% of cases performed endovascularly) was associated with fewer adverse outcomes after treatment of unruptured aneurysm (0.83,
P
=0.026). Hospital volume had more of an effect on outcome after aneurysm clipping than after endovascular therapy.

Conclusions—

Hospital procedural volume and the propensity of a hospital to use endovascular therapy are both independently associated with better outcome. Improvement in outcome could be achieved by a program of regionalization and selective referral for the treatment of cerebral aneurysms.
Histopathological Evaluation of Middle Cerebral Artery After Percutaneous Intracranial Transluminal Angioplasty
Authors: Schumacher H. Christian , Tanji Kurenai , Mangla Sundeep , Meyers Philip , Pile-Spellman John , Hays Arthur P. , Mohr J.P.
Published: August 2003

Background—

Intracranial atherosclerosis accounts for 8% to 10% of all ischemic strokes, and intracranial angioplasty is increasingly performed to treat stenotic lesions. We report an autopsy case and discuss the effects of intracranial angioplasty for atherosclerotic arteries.

Case Description—

A 77-year-old patient died 9 days after angioplasty of the left middle cerebral artery as a result of cardiorespiratory failure. The patient was anticoagulated before, during, and after the procedure with heparin, aspirin, and clopidogrel. At the site of angioplasty, the densely fibrotic eccentric plaque was displaced from the adjacent media into the lumen, distorting it and forming elongated projections. No local thrombosis, plaque compression, or inflammation was observed. Additionally, an intramural hemorrhage extended from the site of angioplasty into the stenotic proximal inferior division of the left middle cerebral artery.

Conclusions—

Histopathological findings after intracranial angioplasty parallel those in other arterial territories. The implications of these pathological findings on the medical and endovascular treatment of intracranial atherosclerosis are discussed.
Craniotomy for Treatment of Unruptured Aneurysms Is Not Associated With Long-Term Cognitive Dysfunction
Authors: Tuffiash Elizabeth , Tamargo Rafael J. , Hillis Argye E.
Published: August 2003

Background and Purpose—

Many studies have reported frequent cognitive deficits associated with subarachnoid hemorrhage (SAH) and aneurysm repair. One study found more severe cognitive deficits after clipping than coiling of aneurysms, raising the possibility that deficits are due to surgery instead of SAH itself. This possibility was directly addressed by evaluating the cognitive effects of surgery without SAH. The goal of this study was to identify changes in cognitive function associated with surgical clipping of unruptured intracerebral aneurysms.

Methods—

A consecutive series of 25 patients who underwent surgical clipping of ≥1 unruptured intracerebral aneurysm were tested within 1 week preoperatively and again postoperatively (before hospital discharge and at 3-month follow-up if they had deficits at discharge) on a neuropsychological battery. Different forms of each test were used preoperatively and postoperatively to reduce practice effects. Paired
t
tests were used to examine differences between preoperative and postoperative test scores across individuals.

Results—

On most tests, there was no significant change between preoperative and postoperative scores. A significant decline in accuracy before hospital discharge was found only in figure copying (
P
<0.04) and associative learning (
P
<0.01), and significant slowing was found on 1 test (
P
<0.01). Even on these tests, only 3 of 25 patients showed significant deterioration. All but 1 patient returned to baseline by the 3-month follow-up.

Conclusions—

We found no evidence of subtle cognitive deficits resulting from aneurysm clipping alone, suggesting that the common impairments after surgery for ruptured aneurysms are due to SAH itself, complications of SAH such as vasospasm or hydrocephalus, or perioperative stroke.