bluuebunny/crossref_metadata_2025 huggingface dataset:
Unifying the Epidemiological and Evolutionary Dynamics of Pathogens
Authors: Grenfell Bryan T. , Pybus Oliver G. , Gog Julia R. , Wood James L. N. , Daly Janet M. , Mumford Jenny A. , Holmes Edward C.
Published: January 2004

A key priority for infectious disease research is to clarify how pathogen genetic variation, modulated by host immunity, transmission bottlenecks, and epidemic dynamics, determines the wide variety of pathogen phylogenies observed at scales that range from individual host to population. We call the melding of immunodynamics, epidemiology, and evolutionary biology required to achieve this synthesis pathogen “phylodynamics.” We introduce a phylodynamic framework for the dissection of dynamic forces that determine the diversity of epidemiological and phylogenetic patterns observed in RNA viruses of vertebrates. A central pillar of this model is the Evolutionary Infectivity Profile, which captures the relationship between immune selection and pathogen transmission.
Heterodimeric GTPase Core of the SRP Targeting Complex
Authors: Focia Pamela J. , Shepotinovskaya Irina V. , Seidler James A. , Freymann Douglas M.
Published: January 2004

Two structurally homologous guanosine triphosphatase (GTPase) domains interact directly during signal recognition particle (SRP)–mediated cotranslational targeting of proteins to the membrane. The 2.05 angstrom structure of a complex of the NG GTPase domains of Ffh and FtsY reveals a remarkably symmetric heterodimer sequestering a composite active site that contains two bound nucleotides. The structure explains the coordinate activation of the two GTPases. Conformational changes coupled to formation of their extensive interface may function allosterically to signal formation of the targeting complex to the signal-sequence binding site and the translocon. We propose that the complex represents a molecular “latch” and that its disengagement is regulated by completion of assembly of the GTPase active site.
Guar Seed ß-Mannan Synthase Is a Member of the Cellulose Synthase Super Gene Family
Authors: Dhugga Kanwarpal S. , Barreiro Roberto , Whitten Brad , Stecca Kevin , Hazebroek Jan , Randhawa Gursharn S. , Dolan Maureen , Kinney Anthony J. , Tomes Dwight , Nichols Scott , Anderson Paul
Published: January 2004

Genes for the enzymes that make plant cell wall hemicellulosic polysaccharides remain to be identified. We report here the isolation of a complementary DNA (cDNA) clone encodingone such enzyme, mannan synthase (ManS), that makes the β-1, 4-mannan backbone of galactomannan, a hemicellulosic storage polysaccharide in guar seed endosperm walls. The soybean somatic embryos expressing
ManS
cDNA contained high levels of ManS activities that localized to Golgi. Phylogenetically, ManS is closest to group A of the cellulose synthase–like (Csl) sequences from
Arabidopsis
and rice. Our results provide the biochemical proof for the involvement of the
Csl
genes in β-glycan formation in plants.
Inferences on Flow at the Base of Earth's Mantle Based on Seismic Anisotropy
Authors: Panning Mark , Romanowicz Barbara
Published: January 2004

We applied global waveform tomography to model radial anisotropy in the whole mantle. We found that in the last few hundred kilometers near the core-mantle boundary, horizontally polarized
S
-wave velocities (

V
SH

) are, on average, faster (by ∼1%) than vertically polarized
S
-wave velocities (

V
SV

), suggesting a large-scale predominance of horizontal shear. This confirms that the
D
″ region at the base of the mantle is also a mechanical boundary layer for mantle convection. A notable exception to this average signature can be found at the base of the two broad low-velocity regions under the Pacific Ocean and under Africa, often referred to as “superplumes,” where the anisotropic pattern indicates the onset of vertical flow.
Satellite Measurements Reveal Persistent Small-Scale Features in Ocean Winds
Authors: Chelton Dudley B. , Schlax Michael G. , Freilich Michael H. , Milliff Ralph F.
Published: January 2004

Four-year averages of 25-kilometer-resolution measurements of near-surface wind speed and direction over the global ocean from the QuikSCAT satellite radar scatterometer reveal the existence of surprisingly persistent small-scale features in the dynamically and thermodynamically important curl and divergence of the wind stress. Air-sea interaction over sea surface temperature fronts throughout the world ocean is evident in both the curl and divergence fields, as are the influences of islands and coastal mountains. Ocean currents such as the Gulf Stream generate distinctive patterns in the curl field. These previously unresolved features have important implications for oceanographic and air-sea interaction research.
EGF-Like Growth Factors As Mediators of LH Action in the Ovulatory Follicle
Authors: Park Jy-Young , Su You-Qiang , Ariga Miyako , Law Evelyn , Jin S.-L. Catherine , Conti Marco
Published: January 2004

Before ovulation in mammals, a cascade of events resembling an inflammatory and/or tissue remodeling process is triggered by luteinizing hormone (LH) in the ovarian follicle. Many LH effects, however, are thought to be indirect because of the restricted expression of its receptor. Here, we demonstrate that LH stimulation induces the transient and sequential expression of the epidermal growth factor (EGF) family members amphiregulin, epiregulin, and beta-cellulin. Incubation of follicles with these growth factors recapitulates the morphological and biochemical events triggered by LH, including cumulus expansion and oocyte maturation. Thus, these EGF-related growth factors are paracrine mediators that propagate the LH signal throughout the follicle.
Multiple Ebola Virus Transmission Events and Rapid Decline of Central African Wildlife
Authors: Leroy Eric M. , Rouquet Pierre , Formenty Pierre , Souquière Sandrine , Kilbourne Annelisa , Froment Jean-Marc , Bermejo Magdalena , Smit Sheilag , Karesh William , Swanepoel Robert , Zaki Sherif R. , Rollin Pierre E.
Published: January 2004

Several human and animal Ebola outbreaks have occurred over the past 4 years in Gabon and the Republic of Congo. The human outbreaks consisted of multiple simultaneous epidemics caused by different viral strains, and each epidemic resulted from the handling of a distinct gorilla, chimpanzee, or duiker carcass. These animal populations declined markedly during human Ebola outbreaks, apparently as a result of Ebola infection. Recovered carcasses were infected by a variety of Ebola strains, suggesting that Ebola outbreaks in great apes result from multiple virus introductions from the natural host. Surveillance of animal mortality may help to predict and prevent human Ebola outbreaks.
Self-Assembly of Mesoscopic Metal-Polymer Amphiphiles
Authors: Park Sungho , Lim Jung-Hyurk , Chung Sung-Wook , Mirkin Chad A.
Published: January 2004

The assembly properties of two- and three-component rod-like building blocks consisting of gold and polymer block domains have been investigated. These structures behave like mesoscopic amphiphiles and form a series of single-layer superstructures consisting of bundles, tubes, and sheets depending upon the compositional periodicity. Unlike molecular systems, the template used to initially synthesize them plays a critical role in the assembly process by prealigning them in a manner that facilitates their assembly by optimizing the correct collisional orientation upon dissolution of the template. Tubular structures with tailorable diameters can be assembled in a predictable manner on the basis of an estimate of the hybrid rod packing parameters.
Neonatal Herpes Simplex Infection
Authors: Kimberlin David W.
Published: January 2004

Tremendous advances have occurred over the past 30 years in the diagnosis and management of neonatal herpes simplex virus (HSV) disease. Mortality in patients with disseminated disease has decreased from 85 to 29%, and that in patients with central nervous system (CNS) disease has decreased from 50 to 4%. Morbidity has been improved more modestly: the proportion of patients with disseminated disease who are developing normally at 1 year has increased from 50 to 83%. While the proportion of patients with neurologic morbidity following CNS disease has remained essentially unchanged over the past three decades, the total number of patients who are developing normally following HSV CNS disease has increased due to the improved survival. Although additional therapeutic advances in the future are possible, more immediate methods for further improvements in outcome for patients with this potentially devastating disease lie in an enhanced awareness of neonatal HSV infection and disease. A thorough understanding of the biology and natural history of HSV in the gravid woman and the neonate provides the basis for such an index of suspicion and is provided in this article.
Global Change and Human Vulnerability to Vector-Borne Diseases
Authors: Sutherst Robert W.
Published: January 2004

Global change includes climate change and climate variability, land use, water storage and irrigation, human population growth and urbanization, trade and travel, and chemical pollution. Impacts on vector-borne diseases, including malaria, dengue fever, infections by other arboviruses, schistosomiasis, trypanosomiasis, onchocerciasis, and leishmaniasis are reviewed. While climate change is global in nature and poses unknown future risks to humans and natural ecosystems, other local changes are occurring more rapidly on a global scale and are having significant effects on vector-borne diseases. History is invaluable as a pointer to future risks, but direct extrapolation is no longer possible because the climate is changing. Researchers are therefore embracing computer simulation models and global change scenarios to explore the risks. Credible ranking of the extent to which different vector-borne diseases will be affected awaits a rigorous analysis. Adaptation to the changes is threatened by the ongoing loss of drugs and pesticides due to the selection of resistant strains of pathogens and vectors. The vulnerability of communities to the changes in impacts depends on their adaptive capacity, which requires both appropriate technology and responsive public health systems. The availability of resources in turn depends on social stability, economic wealth, and priority allocation of resources to public health.
Strongyloides stercoralisin the Immunocompromised Population
Authors: Keiser Paul B. , Nutman Thomas B.
Published: January 2004

Strongyloides stercoralis is an intestinal nematode of humans that infects tens of millions of people worldwide. S. stercoralis is unique among intestinal nematodes in its ability to complete its life cycle within the host through an asexual autoinfective cycle, allowing the infection to persist in the host indefinitely. Under some conditions associated with immunocompromise, this autoinfective cycle can become amplified into a potentially fatal hyperinfection syndrome, characterized by increased numbers of infective filariform larvae in stool and sputum and clinical manifestations of the increased parasite burden and migration, such as gastrointestinal bleeding and respiratory distress. S. stercoralis hyperinfection is often accompanied by sepsis or meningitis with enteric organisms. Glucocorticoid treatment and human T-lymphotropic virus type 1 infection are the two conditions most specifically associated with triggering hyperinfection, but cases have been reported in association with hematologic malignancy, malnutrition, and AIDS. Anthelmintic agents such as ivermectin have been used successfully in treating the hyperinfection syndrome as well as for primary and secondary prevention of hyperinfection in patients whose exposure history and underlying condition put them at increased risk.
Staphylococcus aureusCapsular Polysaccharides
Authors: O'Riordan Katherine , Lee Jean C.
Published: January 2004

Serotype 5 and 8 capsular polysaccharides predominate among clinical isolates ofStaphylococcus aureus.The results of experiments in animal models of infection have revealed that staphylococcal capsules are important in the pathogenesis ofS. aureusinfections. The capsule enhances staphylococcal virulence by impeding phagocytosis, resulting in bacterial persistence in the bloodstream of infected hosts.S. aureuscapsules also promote abscess formation in rats. Although the capsule has been shown to modulateS. aureusadherence to endothelial surfaces in vitro, animal studies suggest that it also promotes bacterial colonization and persistence on mucosal surfaces.S. aureuscapsular antigens are surface associated, limited in antigenic specificity, and highly conserved among clinical isolates. With the emergence of vancomycin-resistantS. aureusin the United States in 2002, new strategies are needed to combat staphylococcal infections. Purified serotype 5 and 8 capsular polysaccharides offer promise as target antigens for a vaccine to prevent staphylococcal infections, although the inclusion of other antigens is likely to be essential in the development of an effectiveS. aureusvaccine. The genetics and mechanisms of capsule biosynthesis are complex, and much work remains to enhance our understanding of capsule biosynthesis and its regulation.
History, Dynamics, and Public Health Importance of Malaria Parasite Resistance
Authors: Talisuna Ambrose O. , Bloland Peter , D’Alessandro Umberto
Published: January 2004

Despite considerable efforts, malaria is still one of the most devastating infectious diseases in the tropics. The rapid spread of antimalarial drug resistance currently compounds this grim picture. In this paper, we review the history of antimalarial drug resistance and the methods for monitoring it and assess the current magnitude and burden of parasite resistance to two commonly used drugs: chloroquine and sulfadoxine-pyrimethamine. Furthermore, we review the factors involved in the emergence and spread of drug resistance and highlight its public health importance. Finally, we discuss ways of dealing with such a problem by using combination therapy and suggest some of the research themes needing urgent answers.
Infection Control in Cystic Fibrosis
Authors: Saiman Lisa , Siegel Jane
Published: January 2004

Over the past 20 years there has been a greater interest in infection control in cystic fibrosis (CF) as patient-to-patient transmission of pathogens has been increasingly demonstrated in this unique patient population. The CF Foundation sponsored a consensus conference to craft recommendations for infection control practices for CF care providers. This review provides a summary of the literature addressing infection control in CF.
Burkholderia cepacia
complex,
Pseudomonas aeruginosa
, and
Staphylococcus aureus
have all been shown to spread between patients with CF.
Standard precautions
,
transmission-based precautions
including contact and droplet precautions, appropriate hand hygiene for health care workers, patients, and their families, and care of respiratory tract equipment to prevent the transmission of infectious agents serve as the foundations of infection control and prevent the acquisition of potential pathogens by patients with CF. The respiratory secretions of all CF patients potentially harbor clinically and epidemiologically important microorganisms, even if they have not yet been detected in cultures from the respiratory tract. CF patients should be educated to contain their secretions and maintain a distance of >3 ft from other CF patients to avoid the transmission of potential pathogens, even if culture results are unavailable or negative. To prevent the acquisition of pathogens from respiratory therapy equipment used in health care settings as well as in the home, such equipment should be cleaned and disinfected. It will be critical to measure the dissemination, implementation, and potential impact of these guidelines to monitor changes in practice and reduction in infections.
Cryptosporidium
Taxonomy: Recent Advances and Implications for Public Health
Authors: Xiao Lihua , Fayer Ronald , Ryan Una , Upton Steve J.
Published: January 2004

There has been an explosion of descriptions of new species of Cryptosporidium during the last two decades. This has been accompanied by confusion regarding the criteria for species designation, largely because of the lack of distinct morphologic differences and strict host specificity among Cryptosporidium spp. A review of the biologic species concept, the International Code of Zoological Nomenclature (ICZN), and current practices for Cryptosporidium species designation calls for the establishment of guidelines for naming Cryptosporidium species. All reports of new Cryptosporidium species should include at least four basic components: oocyst morphology, natural host specificity, genetic characterizations, and compliance with the ICZN. Altogether, 13 Cryptosporidium spp. are currently recognized: C. muris, C. andersoni, C. parvum, C. hominis, C. wrairi, C. felis, and C. cannis in mammals; C. baïleyi, C. meleagridis, and C. galli in birds; C. serpentis and C. saurophilum in reptiles; and C. molnari in fish. With the establishment of a framework for naming Cryptosporidium species and the availability of new taxonomic tools, there should be less confusion associated with the taxonomy of the genus Cryptosporidium. The clarification of Cryptosporidium taxonomy is also useful for understanding the biology of Cryptosporidium spp., assessing the public health significance of Cryptosporidium spp. in animals and the environment, characterizing transmission dynamics, and tracking infection and contamination sources.
Health Impacts of Environmental Mycobacteria
Authors: Primm Todd P. , Lucero Christie A. , Falkinham Joseph O.
Published: January 2004

Environmental mycobacteria are emerging pathogens causing opportunistic infections in humans and animals. The health impacts of human-mycobacterial interactions are complex and likely much broader than currently recognized. Environmental mycobacteria preferentially survive chlorination in municipal water, using it as a vector to infect humans. Widespread chlorination of water has likely selected more resistant environmental mycobacteria species and potentially explains the shift from
M. scrofulaceum
to
M. avium
as a cause of cervical lymphadenitis in children. Thus, human activities have affected mycobacterial ecology. While the slow growth and hydrophobicity of environmental mycobacteria appear to be disadvantages, the unique cell wall architecture also grants high biocide and antibiotic resistance, while hydrophobicity facilitates nutrient acquisition, biofilm formation, and spread by aerosolization. The remarkable stress tolerance of environmental mycobacteria is the major reason they are human pathogens. Environmental mycobacteria invade protozoans, exhibiting parasitic and symbiotic relationships. The molecular mechanisms of mycobacterial intracellular pathogenesis in animals likely evolved from similar mechanisms facilitating survival in protozoans. In addition to outright infection, environmental mycobacteria may also play a role in chronic bowl diseases, allergies, immunity to other pulmonary infections, and the efficacy of bacillus Calmette-Guerin vaccination.
CENTRAL CHARGES AND EFFECTIVE ACTION AT FINITE TEMPERATURE AND DENSITY
Authors: GAMBOA J. , LÓPEZ-SARRIÓN J. , LOEWE M. , MÉNDEZ F.
Published: January 2004

The current algebra for gauge theories like QCD at finite temperature and density is studied. We start considering, the massless Thirring model at finite temperature and density, finding an explicit expression for the current algebra. The central charge only depends on the coupling constant and there are not new effects due to temperature and density. From this calculation, we argue how to compute the central charge for QCD4 and we argue why the central charge in four dimensions could be modified by finite temperature and density.
FLAVOR VIOLATION FROM Z PENGUINS IN THE LEFT–RIGHT SUPERSYMMETRIC MODEL
Authors: FRANK MARIANA
Published: January 2004

We analyze the effects of flavor-changing ZL penguin diagrams on rare kaon decays in a left–right supersymmetric model (LRSUSY). Using the mass-insertion approximation and including up to second-order effects, we show that the constraints obtained on up-sector flavor violating parameters can be stronger than previous bounds. These effects present a sensitive test of an extended gauge sector in supersymmetry and can be used to distinguish LRSUSY from other supersymmetric models.
EFFECTIVE MASS OF A RADIATING CHARGED PARTICLE IN EINSTEIN'S UNIVERSE
Authors: VAGENAS ELIAS C.
Published: January 2004

The effective gravitational mass as well as the energy and momentum distributions of a radiating charged particle in Einstein's universe are evaluated. The Møller's energy–momentum complex is employed for this computation. The spacetime under study is a generalization of Bonnor and Vaidya spacetime in the sense that the metric is described in the cosmological background of Einstein's universe in lieu of the flat background. Several spacetimes are limiting cases of the one considered here. In particular for the Reissner–Nordström black hole background, our results are exactly the same as those derived by Cohen and Gautreau using Whittaker's theorem and by Cohen and de Felice using Komar's mass. Furthermore, the power output for the spacetime under consideration is obtained.
OPTIMIZATION OF HEAT TREATMENTS OF VIETNAMESE RUBIES
Authors: WINOTAI P. , LIMSUWAN P. , RITTIKULSITTICHAI S.
Published: January 2004

A suitable heating condition designed for a particular type of ruby is used to enhance the quality to increase its value. Heating Vietnamese rubies in an oxygen atmosphere may improve color and clarity, and thus increase their prices. The color of rubies is due to the presence of trace amounts of Cr 3+. Fe 3+ yields a pale yellow color and the charge transfer mechanism between Fe 2+ and Ti 4+ gives ruby an undesirable bluish color. Reducing this mechanism is possible by heating the ruby in oxygen so that most of the Fe 2+ is converted into Fe 3+ ions and thus they appear a more intense red. By using XRD we found that the c/a ratio of the hexagonal structure was smallest after heat treatment at 1300°C. The number of Fe 2+ ions converted to Fe 3+ was detected by an electron spin resonance spectrometer and found to increase with temperature. The ruby appeared a most intense red after heating at 1500°C for 12 hours. The color change is due to both the decrease in c/a ratio and the increase in the number of Fe 3+ ions. ESR experiments on ruby crystals by rotation about their c-axis show that Fe 3+ ions are a little off axis before heat treatment. After heat treatment at 1300°C they move to new asymmetric equilibrium positions towards larger O 2- triangles. It is not clear, however, if this Fe 3+ movement is related to the change in color. The asymmetry may arise due to some O2- vacancies.
SOLUTION OF CAMERA REGISTRATION PROBLEM VIA 3D-2D PARAMETERIZED MODEL MATCHING FOR ON-ROAD NAVIGATION
Authors: HU ZHENCHENG , UCHIMURA KEIICHI
Published: January 2004

This paper presents a dynamical solution of camera registration problem for on-road navigation applications via a 3D-2D parameterized model matching algorithm. The traditional camera'fs three dimensional (3D) position and pose estimation algorithms have always employed fixed and known-structure models as well as the depth information to obtain the 3D-2D correlations, which is however unavailable for on-road navigation applications since there are no fixed models in the general road scene. With the constraints of road structure and on-road navigation features, this paper presents a 2D digital road-based road shape modeling algorithm. Dynamically generated multi-lane road shape models are used to match real road scenes to estimate the camera 3D position and pose data. Our algorithms have successfully simplified the 3D-2D correlation problem to the 2D-2D road model matching on the projective image. The algorithms proposed in this paper are validated with the experimental results of real road tests under different conditions and types of road.
FAST AND ACCURATE STEREO VISION-BASED ESTIMATION OF 3D POSITION AND AXIAL MOTION OF ROAD OBSTACLES
Authors: TOULMINET GWENAËLLE , MOUSSET STÉPHANE , BENSRHAIR ABDELAZIZ
Published: January 2004

In this article, we present a fast and accurate stereo vision-based system that detects and tracks road obstacles, as well as computes their 3D position and their axial motion. To do so, axial motion maps are constructed and the inclination angles of 3D straight segments are computed. 3D straight segments are obtained after the construction of 3D sparse maps based on dynamic programming and multi-criteria analysis. Axial motion maps are computed from a sequence of dense 3D maps without region matching.
MESH COMPARISON USING ATTRIBUTE DEVIATION METRIC
Authors: ROY MICHAËL , FOUFOU SEBTI , TRUCHETET FRÉDÉRIC
Published: January 2004

We propose a mesh comparison method using a new attribute deviation metric. The considered meshes contain geometrical and appearance attributes (material color, texture, temperature, etc.). The proposed deviation metric computes local differences between the attributes of two meshes. A mesh comparison assessment can be done easily and quickly using this metric. The techniques proposed are applicable in a number of ways, e.g. 3D matching and registration, and the example described in the paper is the simplification of a surface by iteratively reducing its complexity according to an error metric. The results are presented showing the success of the algorithm through comparisons with other measures and with three different simplification algorithms.
On hypersurfaces in a locally affine Riemannian Banach manifold II
Authors: Lashin El-Said R. , Mersal Tarek F.
Published: January 2004

In our previous work (2002), we proved that an
essential second‐order hypersurface in an infinite‐dimensional
locally affine Riemannian Banach manifold is a Riemannian
manifold of constant nonzero curvature. In this note, we prove
the converse, in other words, we prove that a hypersurface of
constant nonzero Riemannian curvature in a locally affine (flat)
semi‐Riemannian Banach space is an essential hypersurface of
second order.
Stability of reaction fronts in thin domains
Authors: Agouzal A. , Boujena S. , Ciuperca I. , Volpert V.
Published: January 2004

The paper is devoted to the stability of reaction fronts in thin
domains. The influence of natural convection and of heat losses
through the walls of the reactor is studied numerically and
analytically. Critical conditions of stability of stationary
solutions are obtained.
On embedding properties of SD‐groups
Authors: Mikaelian Vahagn H.
Published: January 2004

Continuing our recent research on embedding properties of
generalized soluble and generalized nilpotent groups, we study
some embedding properties of SD‐groups. We show that every
countable SD‐group G can be subnormally embedded into a
two‐generator SD‐group H. This embedding can have additional
properties: if the group G is fully ordered, then the group H
can be chosen to be also fully ordered. For any nontrivial word
set V, this embedding can be constructed so that the image of
G under the embedding lies in the verbal subgroup V(H) of
H. The main argument of the proof is used to build continuum
examples of SD‐groups which are not locally soluble.
Inclusion results for convolution submethods
Authors: Osikiewicz Jeffrey A. , Khan Mohammad K.
Published: January 2004

If B is a summability matrix, then the submethod Bλ is
the matrix obtained by deleting a set of rows from the matrix
B. Comparisons between Euler‐Knopp submethods and the Borel
summability method are made. Also, an equivalence result for
convolution submethods is established. This result will
necessarily apply to the submethods of the Euler‐Knopp, Taylor,
Meyer‐König, and Borel matrix summability methods.
On uniform Kadec‐Klee properties and rotundity in generalized Cesàro sequence spaces
Authors: Petrot Narin , Suantai Suthep
Published: January 2004

We consider the generalized Cesàro sequence spaces defined by Suantai (2003) and consider it equipped with the
Amemiya norm. The main purpose of this paper is to show that
ces(p) equipped with the Amemiya norm is rotund
and has uniform Kadec‐Klee property.
Risk of Myocardial Infarction and Stroke in Smokers Is Related to Plasma Levels of Inflammation-Sensitive Proteins
Authors: Lind P. , Engström G. , Stavenow L. , Janzon L. , Lindgärde F. , Hedblad B.
Published: January 2004

Background—

The extent to which differences in cardiovascular risk between smokers with similar daily tobacco consumption may be related to plasma levels of inflammation-sensitive proteins (ISP) and whether these proteins are associated with levels of carboxyhemoglobin (COHb%) have not been clarified.

Methods and Results—

In a population-based cohort of 1489 never smokers, 1685 former smokers, and 2901 current smokers, aged 28 to 61 years, plasma levels of orosomucoid (α
1
-acid glycoprotein), α
1
-antitrypsin, haptoglobin, fibrinogen, and ceruloplasmin were measured. COHb% levels were available for 2098 of them. Incidence of myocardial infarction, stroke, and death were monitored over 18.7±4.7 years. The proportion with high ISP levels (ie, ≥2 ISP in the top quartile) increased progressively with daily tobacco consumption (
P
<0.01) and COHb% (
P
<0.01). In all smoking categories, the incidence of stroke, cardiac events, and death was related to ISP. In heavy smokers, high ISP levels were associated with adjusted relative risks of 1.57 (1.05 to 2.35) and 1.50 (1.11 to 2.03) for cardiac events and death, respectively. Corresponding figures for moderate and light smokers were 1.59 (1.13 to 2.24) and 1.14 (0.87 to 1.49), respectively, and 1.32 (0.95 to 1.85) and 1.48 (1.10 to 1.98), respectively.

Conclusion—

ISP levels are related to COHb% in smokers. High levels are associated with an increased cardiovascular risk.
Molecular Mechanism for Changes in Proteoglycan Binding on Compositional Changes of the Core and the Surface of Low-Density Lipoprotein–Containing Human Apolipoprotein B100
Authors: Flood Christofer , Gustafsson Maria , Pitas Robert E. , Arnaboldi Lorenzo , Walzem Rosemary L. , Borén Jan
Published: January 2004

Objective—

The aim of this study was to investigate the molecular mechanism for changes in proteoglycan binding and LDL receptor affinity on two compositional changes in LDL that have been associated with atherosclerosis: cholesterol enrichment of the core and modification by secretory group IIA phospholipase A2 (sPLA
2
) of the surface.

Methods and Results—

Transgenic mice expressing recombinant apolipoprotein (apo) B and sPLA
2
were generated. Recombinant LDL were isolated and tested for their proteoglycan and LDL receptor-binding activity. The results show site A (residues 3148-3158) in apoB100 becomes functional in sPLA
2
-modified LDL and that site A acts cooperatively with site B (residues 3359-3369), the primary proteoglycan-binding site in native LDL, in the binding of sPLA
2
-modified LDL to proteoglycans. Our results also show that cholesterol enrichment of LDL is associated with increased affinity for proteoglycans and for the LDL receptor. This mechanism is likely mediated by a conformational change of site B and is independent of site A in apoB100.

Conclusion—

Site A in apoB100 becomes functional in sPLA
2
-modified LDL and acts cooperatively with site B resulting in increased proteoglycan-binding activity. The increased binding for proteoglycans of cholesterol-enriched LDL is solely dependent on site B.
Regulation of Endopeptidases EC3.4.24.15 and EC3.4.24.16 in Vascular Endothelial Cells by Cyclic Strain: Role of Gi Protein Signaling
Authors: Cotter Eoin J. , Sweeney Nicholas von Offenberg , Coen Paul M. , Birney Yvonne A. , Glucksman Marc J. , Cahill Paul A. , Cummins Philip M.
Published: January 2004

Objective—

Endopeptidase EC3.4.24.15 (EP24.15)- and EC3.4.24.16 (EP24.16)-specific peptide hydrolysis plays an important role in endothelium-mediated vasoregulation. Given the significant influence of hemodynamic forces on vascular homeostasis and pathology, we postulated that these related peptidases may be mechanosensitive. The objective of this study, therefore, was to investigate the putative role of cyclic strain in regulating the expression and enzymatic activity of EP24.15 and EP24.16 in bovine aortic endothelial cells (BAECs).

Methods and Results—

BAECs were cultured under conditions of defined cyclic strain (0% to 10% stretch, 60 cycles/min, 0 to 24 hours). Strain significantly increased EP24.15 and EP24.16 soluble activity in a force- and time-dependent manner, with elevations of 2.3±0.4- and 1.9±0.3-fold for EP24.15 and EP24.16, respectively, after 24 hours at 10% strain. Pharmacological agents and dominant-negative G protein mutants used to selectively disrupt Gi
α
- and Gβγ-mediated signaling pathways attenuated strain-dependent (24 hours, 5%) increases for both enzymes. Differences in the inhibitory profile for both enzymes were also noted, with EP24.15 displaying greater sensitivity to Gi
α2/3
inhibition and EP24.16 exhibiting greater sensitivity to Gi
α1/2
and Gβγ inhibition. Cyclic strain also increased levels of secreted EP24.15 and EP24.16 activity by 2.6±0.02- and 3.6±0.2-fold, respectively, in addition to mRNA levels for both enzymes (EP24.15 +42%, EP24.16 +56%).

Conclusions—

Our findings suggest that cyclic strain putatively regulates both the mRNA expression and enzymatic function of EP24.15 and EP24.16 in BAECs via alternate Gi protein signaling pathways.
Polymorphism of the Soluble Epoxide Hydrolase Is Associated With Coronary Artery Calcification in African-American Subjects
Authors: Fornage Myriam , Boerwinkle Eric , Doris Peter A. , Jacobs David , Liu Kiang , Wong Nathan D.
Published: January 2004

Background—

Modulation of endogenous epoxide levels by soluble epoxide hydrolase (sEH) in the endothelium represents an important mechanism in the regulation of cardiovascular function. We examined the relationship between a common, functional polymorphism of the human sEH gene and coronary artery calcification (CAC) in young, largely asymptomatic African-American and non-Hispanic white subjects.

Methods and Results—

Multiple logistic regression and Tobit regression models were used to assess the relationship between the sEH Arg287Gln polymorphism and presence and quantity of CAC. Models adjusting for race (except in race-specific analyses), age, sex, smoking, body mass index, systolic blood pressure, LDL cholesterol, and HDL cholesterol were estimated. Allele and genotype frequency distributions were not significantly different between the 2 ethnic groups (
P
=0.22;
P
=0.17, respectively). The Arg287Gln polymorphism of the sEH gene was a significant predictor of CAC status in African-American participants, either alone or after adjusting for other risk factors. African-American subjects with at least 1 copy of the Gln287 allele had a 2-fold greater risk of having CAC compared with those not carrying this allele (95% CI, 1.1 to 2.9;
P
=0.02). There was no relationship between Arg287Gln polymorphism and the probability of having CAC in white participants (OR, 0.8; 95% CI, 0.5 to 1.3;
P
=0.49). Inferences from multivariable Tobit regression were similar to those obtained in the logistic regression models, indicating that the Arg287Gln polymorphism was a significant independent predictor of both presence and quantity of CAC in African-American but not white subjects.

Conclusions—

These data suggest an intriguing and possibly novel role for sEH in the pathogenesis of atherosclerosis, which deserves additional investigation.
Five-Year Follow-Up After Intracoronary Gamma Radiation Therapy for In-Stent Restenosis
Authors: Waksman Ron , Ajani Andrew E. , White R. Lawrence , Chan Rosanna , Bass Bill , Pichard Augusto D. , Satler Lowell F. , Kent Kenneth M. , Torguson Rebecca , Deible Regina , Pinnow Ellen , Lindsay Joseph
Published: January 2004

Background—

The Washington Radiation for In-Stent Restenosis Trial is a double-blinded randomized study evaluating the effects of intracoronary radiation therapy (IRT) in patients with in-stent restenosis (ISR).

Methods and Results—

One hundred thirty patients with ISR (100 native coronary and 30 vein grafts) underwent percutaneous transluminal coronary angioplasty, laser ablation, rotational atherectomy, or additional stenting (36% of lesions). Patients were randomized to either 192-Iridium IRT or placebo, with a prescribed dose of 15 Gy to a 2-mm radial distance from the center of the source. Angiographic restenosis (27% versus 56%,
P
=0.002) and target vessel revascularization (26% versus 68%,
P
<0.001) were reduced at 6 months in patients treated with IRT. Between 6 and 60 months, patients treated with IRT compared with placebo had more target lesion revascularization (IRT, 21.6% versus placebo, 4.7%;
P
=0.04) and target vessel revascularization (IRT, 21.5% versus placebo, 6.1%;
P
=0.03). At 5 years, the major adverse cardiac event rate was significantly reduced with IRT (46.2% versus 69.2%,
P
=0.008).

Conclusions—

In the Washington Radiation for In-Stent Restenosis Trial, patients with ISR treated with IRT using 192-Iridium had a reduction in the need for repeat target lesion and vessel revascularization at 6 months and 5 years.
Effects of Off-Pump Versus On-Pump Coronary Surgery on Reversible and Irreversible Myocardial Injury
Authors: Selvanayagam Joseph B. , Petersen Steffen E. , Francis Jane M. , Robson Matthew D. , Kardos Attila , Neubauer Stefan , Taggart David P.
Published: January 2004

Background—

There is biochemical evidence that off-pump coronary artery bypass grafting (OPCABG) reduces myocardial injury compared with the use of cardiopulmonary bypass (ONCABG), but the functional significance of this is uncertain. We hypothesized that OPCABG surgery would result in reduced postoperative reversible (stunning) and irreversible myocardial injury, as assessed by cardiovascular MRI (CMRI).

Methods and Results—

In a single-center randomized trial, 60 patients undergoing multivessel total arterial revascularization were randomly assigned: 30 to OPCABG and 30 to ONCABG. Patients underwent preoperative and early postoperative cine MRI for assessment of global left ventricular function, and contrast-enhanced CMRI for assessment of irreversible myocardial injury. Serial troponin I measurements were obtained perioperatively and correlated with the CMRI findings. The mean preoperative cardiac index was similar in the 2 surgical groups (2.9±0.7 ONCABG; 2.9±0.8 OPCABG;
P
=0.9). After surgery, the cardiac index was significantly higher in the OPCABG group (2.7±0.6 ONCABG; 3.2±0.8 OPCABG;
P
=0.04). New irreversible myocardial injury was similar in incidence (36% ONCABG; 44% OPCABG;
P
=0.8) and magnitude (6.3±3.6 g ONCABG; 6.8±4.0 g OPCABG;
P
=0.9) across the 2 groups. The median area-under-the-curve (AUC) troponin I values were significantly larger in the ONCABG group (182 versus 135 μg/L;
P
=0.02). There was a moderate correlation between the troponin I AUC values and mean mass of new myocardial hyperenhancement (
r
2
=0.4;
P
=0.008).

Conclusions—

OPCABG results in significantly better left ventricular function early after surgery but does not reduce the incidence or extent of irreversible myocardial injury.
Amiodarone Therapy for Drug-Refractory Fetal Tachycardia
Authors: Strasburger Janette F. , Cuneo Bettina F. , Michon Maaike M. , Gotteiner Nina L. , Deal Barbara J. , McGregor Scott N. , Oudijk Martijn A. , Meijboom Erik J. , Feinkind Leonard , Hussey Michael , Parilla Barbara V.
Published: January 2004

Background—

Fetal tachycardia complicated by ventricular dysfunction and hydrops fetalis carries a significant risk of morbidity and mortality. Transplacental digoxin is effective therapy in a small percentage, but there is no consensus with regard to antiarrhythmic treatment if digoxin fails. This study evaluates the safety, efficacy, and outcome of amiodarone therapy for digoxin-refractory fetal tachycardia with heart failure.

Methods and Results—

Fetuses with incessant tachycardia and either hydrops fetalis (n=24) or ventricular dysfunction (n=2) for whom digoxin monotherapy and secondary antiarrhythmic agents (n=13) were not effective were treated transplacentally with a loading dose of oral amiodarone for 2 to 7 days, followed by daily maintenance therapy for <1 to 15 weeks. Digoxin therapy was continued throughout gestation. Newborns were studied by transesophageal pacing or ECG monitoring to determine the mechanism of tachycardia. Three fetuses were delivered urgently in tachycardia during amiodarone loading, and 3 required additional antiarrhythmic agents for sustained cardioversion. Amiodarone or amiodarone combinations converted 14 of 15 (93%) with reentrant supraventricular tachycardia, 2 of 2 with ventricular or junctional ectopic tachycardia, and 3 of 9 (33%) with atrial flutter. Amiodarone-related adverse effects were transient in 5 infants and 8 mothers. Mean gestational age at delivery was 37 weeks, with 100% survival.

Conclusions—

Orally administered amiodarone is safe and effective treatment for drug-refractory fetal tachycardia, specifically reentrant supraventricular tachycardia, junctional ectopic, or ventricular tachycardia, even when accompanied by hydrops fetalis or ventricular dysfunction.
N
-Acetylcysteine Prevents the Deleterious Effect of Tumor Necrosis Factor-α on Calcium Transients and Contraction in Adult Rat Cardiomyocytes
Authors: Cailleret Michel , Amadou Aïssata , Andrieu-Abadie Nathalie , Nawrocki Artur , Adamy Christophe , Ait-Mamar Bouziane , Rocaries François , Best-Belpomme Martin , Levade Thierry , Pavoine Catherine , Pecker Françoise
Published: January 2004

Background—

The negative effect of tumor necrosis factor-α (TNF-α) on heart contraction, which is mediated by sphingosine, is a major component in heart failure. Because the cellular level of glutathione may limit sphingosine production via the inhibition of the Mg-dependent neutral sphingomyelinase (N-SMase), we hypothesized that cardiac glutathione status might determine the negative contractile response to TNF-α.

Methods and Results—

We examined the effects of TNF-α in isolated cardiomyocytes obtained from control rats or rats that were given the glutathione precursor
N
-acetylcysteine (NAC, 100 mg IP per animal). In cardiomyocytes obtained from control rats, 25 ng/mL TNF-α increased reactive oxygen species generation and N-SMase activity (500% and 34% over basal, respectively) and decreased the amplitude of [Ca
2+
]
i
in response to electrical stimulation (22% below basal). NAC treatment increased cardiac glutathione content by 42%. In cardiomyocytes obtained from NAC-treated rats, 25 ng/mL TNF-α had no effect on reactive oxygen species production or N-SMase activity but increased the amplitude of [Ca
2+
]
i
transients and contraction in response to electrical stimulation by 40% to 50% over basal after 20 minutes. This was associated with a hastened relaxation (20% reduction in
t
1/2
compared with basal) and an increased phosphorylation of both Ser
16
- and Thr
17
-phospholamban residues (260% and 115% of maximal isoproterenol effect, respectively).

Conclusions—

It is concluded that cardiac glutathione status, by controlling N-SMase activation, determines the severity of the adverse effects of TNF-α on heart contraction. Glutathione supplementation may therefore provide therapeutic benefits for vulnerable hearts.
Outcomes in Patients With Diabetes Mellitus Undergoing Percutaneous Coronary Intervention in the Current Era
Authors: Mathew Verghese , Gersh Bernard J. , Williams Brent A. , Laskey Warren K. , Willerson James T. , Tilbury R. Thomas , Davis Barry R. , Holmes David R.
Published: January 2004

Background—

Diabetes portends an adverse prognosis in patients undergoing percutaneous coronary intervention (PCI). Whether improvements in current clinical practice (stents, IIb/IIIa antagonists) have resulted in substantial improvement of these outcomes remains an issue. The aim of this study was to determine the influence of diabetes on 9-month outcomes of patients undergoing PCI in the current era.

Methods and Results—

The 11 482 patients enrolled in the Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) Trial were stratified according to the presence (n=2694) or absence (n=8798) of diabetes. Diabetic patients were older; were more likely to be female; had a higher proportion of congestive failure, hypertension, prior CABG, and unstable angina; and had higher body mass index and lower ejection fraction than nondiabetic patients (
P
<0.01 for all comparisons). The degree of multivessel disease was similar between the two groups. American College of Cardiology/American Heart Association type C lesions were more common in diabetic patients (17% versus 15%,
P
<0.01). Angiographic and procedural success rates and in-hospital events were similar between the two groups. The primary end point of death, myocardial infarction, or target vessel revascularization (TVR) was analyzed as time-to-first event within 9 months of the index PCI. After adjusting for certain baseline characteristics, diabetes was independently associated with death at 9 months (relative risk [RR], 1.87; 95% CI, 1.31 to 2.68,
P
<0.01) and with an increased likelihood of TVR (RR, 1.27; 95% CI, 1.14 to 1.42,
P
<0.01), as well as the composite end point of death/myocardial infarction/TVR (RR, 1.26; 95% CI, 1.13 to 1.40,
P
<0.01).

Conclusions—

Despite advances in interventional techniques, diabetes remains a significant independent predictor of adverse events in the intermediate term after PCI.
High Prevalence of Peripheral Arterial Disease in Persons With Renal Insufficiency
Authors: O’Hare Ann M. , Glidden David V. , Fox Caroline S. , Hsu Chi-yuan
Published: January 2004

Background—

Although renal insufficiency is a recognized risk factor for coronary artery disease, little is known about the epidemiology of lower-extremity peripheral arterial disease (PAD) in persons with renal insufficiency.

Methods and Results—

We examined the cross-sectional association of PAD, defined as an ankle-brachial index (ABI) <0.9, and renal insufficiency, defined as an estimated creatinine clearance (CRCL) <60 mL · min
−1
· 1.73 m
−2
, among 2229 eligible participants in the National Health and Nutrition Examination Survey (NHANES) 1999 to 2000. An estimated 1.2±0.3 million persons ≥40 years old with CRCL <60 mL · min
−1
· 1.73 m
−2
(24%) have PAD defined as an ABI <0.9 (versus 3.7% of persons with CRCL ≥60 mL · min
−1
· 1.73 m
−2
). The association of ABI <0.9 with renal insufficiency was independent of potential confounders such as age, diabetes, hypertension, coronary artery disease, stroke history, and hypercholesterolemia (OR 2.5, 95% CI 1.2 to 5.1,
P
=0.011, referent category ABI 1.0 to 1.3).

Conclusions—

Clinicians should be aware of the remarkably high prevalence of PAD among patients with renal insufficiency. In the clinical setting, accurate identification of patients with renal insufficiency combined with routine ABI measurement in this group would greatly enhance efforts to detect subclinical PAD.