bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA Sequence and Mutational Analyses of the pVir Plasmid of
Campylobacter jejuni
81-176
Authors: Bacon David J. , Alm Richard A. , Hu Lan , Hickey Thomas E. , Ewing Cheryl P. , Batchelor Roger A. , Trust Trevor J. , Guerry Patricia
Published: October 2002

The circular pVir plasmid of
Campylobacter jejuni
strain 81-176 was determined to be 37,468 nucleotides in length with a G+C content of 26%. A total of 83% of the plasmid represented coding information, and all but 2 of the 54 predicted open reading frames were encoded on the same DNA strand. There were seven genes on the plasmid in a continguous region of 8.9 kb that encoded orthologs of type IV secretion proteins found in
Helicobacter pylori,
including four that have been described previously (D. J. Bacon, R. A. Alm, D. H. Burr, L. Hu, D. J. Kopecko, C. P. Ewing, T. J. Trust, and P. Guerry, Infect. Immun. 68:4384-4390, 2000). There were seven other pVir-encoded proteins that showed significant similarities to proteins encoded by the plasticity zones of either
H. pylori
J99 or 26695. Mutational analyses of 19 plasmid genes identified 5 additional genes that affect in vitro invasion of intestinal epithelial cells. These included one additional gene encoding a component of a type IV secretion system, an ortholog of Cj0041 from the chromosome of
C. jejuni
NCTC 11168, two
Campylobacter
plasmid-specific genes, and an ortholog of HP0996 from the plasticity zone of
H. pylori
26695.
Phage Therapy of Local and Systemic Disease Caused by
Vibrio vulnificus
in Iron-Dextran-Treated Mice
Authors: Cerveny Karen E. , DePaola Angelo , Duckworth Donna H. , Gulig Paul A.
Published: October 2002

Vibrio vulnificus
is a gram-negative bacterium that contaminates filter-feeding shellfish such as oysters. After ingestion of contaminated oysters, predisposed people may experience highly lethal septicemia. Contamination of wounds with the bacteria can result in devastating necrotizing fasciitis, which can progress to septicemia. The extremely rapid progression of these diseases can render antibiotic treatment ineffective, and death is a frequent outcome. In this study, we examined the potential use of bacteriophages as therapeutic agents against
V. vulnificus
in an iron-dextran-treated mouse model of
V. vulnificus
infection. Mice were injected subcutaneously with 10 times the lethal dose of
V. vulnificus
and injected intravenously, either simultaneously or at various times after infection, with phages. Treatment of mice with phages could prevent death; systemic disease, as measured by CFU per gram of liver and body temperature; and local disease, as measured by CFU per gram of lesion material and histopathologic analysis. Two different phages were effective against three different
V. vulnificus
strains with various degrees of virulence, while a third phage that required the presence of seawater to lyse bacteria in vitro was ineffective at treating mice. Optimum protection required that the phages be administered within 3 h of bacterial inoculation at doses as high as 10
8
PFU. One of the protective phages had a half-life in blood of over 2 h. These results demonstrate that bacteriophages have therapeutic potential for both localized and systemic infections caused by
V. vulnificus
in animals. This model should be useful in answering basic questions regarding phage therapy.
Infection withStrongyloides venezuelensisInduces Transient Airway Eosinophilic Inflammation, an Increase in Immunoglobulin E, and Hyperresponsiveness in Rats
Authors: Silveira Micheline R. , Nunes Kênia P. , Cara Denise C. , Souza Danielle G. , Corrêa Ary , Teixeira Mauro M. , Negrão-Corrêa Deborah
Published: October 2002

Infection by nematode parasites with a pulmonary migration in their life cycle and allergic asthma are two highly prevalent diseases in humans; therefore, one may expect both may occur concomitantly. There is a predominant and essential role of Th2 lymphocytes in the mechanisms underlying the control of parasite elimination as well as in the pathology observed in the asthmatic lung. The consequences of such situations have been explored, with controversial results, justifying the development of experimental models in which the relationship between allergic airway inflammation and helminth infection might be evaluated. The present work describes the inflammatory, humoral, and functional changes that occur in the lung of rats after single (subcutaneous inoculation of 1,500 L3 larvae) or multiple (five weekly subcutaneous inoculations of 1,500 L3 larvae)Strongyloides venezuelensisinfections. The results show that the migration ofS. venezuelensislarvae through the lungs of infected rats induces a local eosinophilic inflammation process which is mostly focal and parenchymal for rats infected a single time and which is peribronchial after multiple infections. The inflammatory process is accompanied by mucus hypersecretion, thickening of bronchial epithelial and muscle layers, and local increase in immunoglobulin E concentrations that peak after 5 to 7 days and are resolved after 12 days of single or multiple infections. The peak of lung immunopathologic changes observed in infected rats coincides with lung airway hyperresponsiveness (AHR), a key functional alteration in asthma. We propose that this experimental model is ideal to carry out further studies on immunoprotection against nematode infection versus immunopathology of allergic airway inflammation.
Intracellular Growth of
Legionella pneumophila
Gives Rise to a Differentiated Form Dissimilar to Stationary-Phase Forms
Authors: Garduño Rafael A. , Garduño Elizabeth , Hiltz Margot , Hoffman Paul S.
Published: October 2002

When
Legionella pneumophila
grows in HeLa cells, it alternates between a replicative form and a morphologically distinct “cyst-like” form termed MIF (mature intracellular form). MIFs are also formed in natural amoebic hosts and to a lesser extent in macrophages, but they do not develop in vitro. Since MIFs accumulate at the end of each growth cycle, we investigated the possibility that they are in vivo equivalents of stationary-phase (SP) bacteria, which are enriched for virulence traits. By electron microscopy, MIFs appeared as short, stubby rods with an electron-dense, laminar outer membrane layer and a cytoplasm largely occupied by inclusions of poly-β-hydroxybutyrate and laminations of internal membranes originating from the cytoplasmic membrane. These features may be responsible for the bright red appearance of MIFs by light microscopy following staining with the phenolic Giménez stain. In contrast, SP bacteria appeared as dull red rods after Giménez staining and displayed a typical gram-negative cell wall ultrastructure. Outer membranes from MIFs and SP bacteria were equivalent in terms of the content of the peptidoglycan-bound and disulfide bond cross-linked OmpS porin, although additional proteins, including Hsp60 (which acts as an invasin for HeLa cells), were detected only in preparations from MIFs. Proteomic analysis revealed differences between MIFs and SP forms; in particular, MIFs were enriched for an ∼20-kDa protein, a potential marker of development. Compared with SP bacteria, MIFs were 10-fold more infectious by plaque assay, displayed increased resistance to rifampin (3- to 5-fold) and gentamicin (10- to 1,000-fold), resisted detergent-mediated lysis, and tolerated high pH. Finally, MIFs had a very low respiration rate, consistent with a decreased metabolic activity. Collectively, these results suggest that intracellular
L. pneumophila
differentiates into a cyst-like, environmentally resilient, highly infectious, post-SP form that is distinct from in vitro SP bacteria. Therefore, MIFs may represent the transmissible environmental forms associated with Legionnaires' disease.
Candida albicansKilling by RAW 264.7 Mouse Macrophage Cells: Effects ofCandidaGenotype, Infection Ratios, and Gamma Interferon Treatment
Authors: Marcil A. , Harcus D. , Thomas D. Y. , Whiteway M.
Published: October 2002

Phagocytic cells such as neutrophils and macrophages are potential components of the immune defense that protects mammals againstCandida albicansinfection. We have tested the interaction between the mouse macrophage cell line RAW 264.7 and a variety of mutant strains ofC. albicans. We used an end point dilution assay to monitor the killing ofC. albicansat low multiplicities of infection (MOIs). Several mutants that show reduced virulence in mouse systemic-infection models show reduced colony formation in the presence of macrophage cells. To permit analysis of the macrophage-Candidainteraction at higher MOIs, we introduced a luciferase reporter gene into wild-type and mutantCandidacells and used loss of the luminescence signal to quantify proliferation. This assay gave results similar to those for the end point dilution assay. Activation of the macrophages with mouse gamma interferon did not enhance anti-Candidaactivity. Continued coculture of theCandidaand macrophage cells eventually led to death of the macrophages, but for the RAW 264.7 cell line this was not due to apoptotic pathways involving caspase-8 or -9 activation. In generalCandidacells defective in the formation of hyphae were both less virulent in animal models and more sensitive to macrophage engulfment and growth inhibition. However the nonvirulent, hypha-defectivecla4mutant line was considerably more resistant to macrophage-mediated inhibition than the wild-type strain. Thus although mutants sensitive to engulfment are typically less virulent in systemic-infection models, sensitivity to phagocytic macrophage cells is not the unique determinant ofC. albicansvirulence.
Shigella flexneri
DegP Facilitates IcsA Surface Expression and Is Required for Efficient Intercellular Spread
Authors: Purdy Georgiana E. , Hong Mei , Payne Shelley M.
Published: October 2002

A
degP
mutant of
Shigella flexneri
was identified in a screen for insertion mutants that invaded cultured cells but did not form wild-type plaques in monolayers. The
degP
mutant SM1100 invaded Henle cells at wild-type levels and induced apoptosis in macrophages but formed smaller plaques than those formed by wild-type
S. flexneri
in confluent monolayers of Henle and Caco-2 cells. The proportion of SM1100 bacteria with IcsA localized to the bacterial pole, a process required for actin polymerization into actin “tails,” was reduced compared to results with wild-type bacteria. The reduction in proper IcsA localization may account for the reduced plaque size of the
degP
mutant. Although DegP is a protease, the protease activity of
S. flexneri
DegP was not required for IcsA localization or the formation of plaques in Henle cell monolayers. DegP was also required for efficient polar IcsA localization in
E. coli
expressing
icsA
. In addition, the growth or survival of SM1100 was compromised compared to that of the wild type at elevated temperatures and in acidic conditions.
Staphylococcus aureus
Aconitase Inactivation Unexpectedly Inhibits Post-Exponential-Phase Growth and Enhances Stationary-Phase Survival
Authors: Somerville Greg A. , Chaussee Michael S. , Morgan Carrie I. , Fitzgerald J. Ross , Dorward David W. , Reitzer Lawrence J. , Musser James M.
Published: October 2002

Staphylococcus aureus
preferentially catabolizes glucose, generating pyruvate, which is subsequently oxidized to acetate under aerobic growth conditions. Catabolite repression of the tricarboxylic acid (TCA) cycle results in the accumulation of acetate. TCA cycle derepression coincides with exit from the exponential growth phase, the onset of acetate catabolism, and the maximal expression of secreted virulence factors. These data suggest that carbon and energy for post-exponential-phase growth and virulence factor production are derived from the catabolism of acetate mediated by the TCA cycle. To test this hypothesis, the aconitase gene was genetically inactivated in a human isolate of
S. aureus
, and the effects on physiology, morphology, virulence factor production, virulence for mice, and stationary-phase survival were examined. TCA cycle inactivation prevented the post-exponential growth phase catabolism of acetate, resulting in premature entry into the stationary phase. This phenotype was accompanied by a significant reduction in the production of several virulence factors and alteration in host-pathogen interaction. Unexpectedly, aconitase inactivation enhanced stationary-phase survival relative to the wild-type strain. Aconitase is an iron-sulfur cluster-containing enzyme that is highly susceptible to oxidative inactivation. We speculate that reversible loss of the iron-sulfur cluster in wild-type organisms is a survival strategy used to circumvent oxidative stress induced during host-pathogen interactions. Taken together, these data demonstrate the importance of the TCA cycle in the life cycle of this medically important pathogen.
Protection against ExperimentalHelicobacter pyloriInfection after Immunization with InactivatedH. pyloriWhole-Cell Vaccines
Authors: Raghavan S. , Hjulström M. , Holmgren J. , Svennerholm A.-M.
Published: October 2002

The protective effect of therapeutic oral immunization with homologous and heterologous formalin-inactivatedHelicobacter pyloricells given together with cholera toxin as an adjuvant was evaluated with C57BL/6 mice infected withH. pyloriSydney strain 1 (SS1). The bacteria used for immunization were strains that were either homologous or heterologous with regard to the O antigen (i.e., the Lewis antigen [Le antigen]) expressed by the lipopolysaccharide of the infectingH. pyloriSS1 strain. We found that repeated oral immunization with inactivatedH. pyloriSS1 cells can significantly inhibit an existing infection (P< 0.001) and that the protection induced by such therapeutic immunization extends to protection against reinfection (P< 0.001). A similar level of protection was also achieved by immunization with another inactivatedH. pyloristrain having the same O antigen (Le antigen) as the infectingH. pyloriSS1 strain. In contrast, immunization with inactivated strains expressing a heterologous O antigen, Lex, provided less protection or no protection. Immunization withH. pylorilysate preparations, on the other hand, resulted in significant comparable protection whether the lysates were prepared from an Lexstrain or an Leystrain. Postimmunization gastritis was seen in mice that were protected after vaccination but not in unimmunized or unprotected mice. In conclusion, therapeutic immunization with inactivatedH. pyloriwhole-cell vaccines may provide strong protection both against experimentalH. pyloriinfection and against later reinfection.
Salmonella enterica
Serovar Typhi Modulates Cell Surface Expression of Its Receptor, the Cystic Fibrosis Transmembrane Conductance Regulator, on the Intestinal Epithelium
Authors: Lyczak Jeffrey B. , Pier Gerald B.
Published: October 2002

The cystic fibrosis transmembrane conductance regulator (CFTR) protein is an epithelial receptor mediating the translocation of
Salmonella enterica
serovar Typhi to the gastric submucosa. Since the level of cell surface CFTR is directly related to the efficiency of serovar Typhi translocation, the goal of this study was to measure CFTR expression by the intestinal epithelium during infection. CFTR protein initially present in the epithelial cell cytoplasm was rapidly trafficked to the plasma membrane following exposure to live serovar Typhi or bacterial extracts. CFTR-dependent bacterial uptake by epithelial cells increased (>100-fold) following CFTR redistribution. The bacterial factor which triggers CFTR redistribution is heat and protease sensitive. These data suggest that serovar Typhi induces intestinal epithelial cells to increase membrane CFTR levels, leading to enhanced bacterial ingestion and submucosal translocation. This could be a key, early step in the infectious process leading to typhoid fever.
Modulation of Inducible Nitric Oxide Synthase Expression by the Attaching and Effacing Bacterial Pathogen
Citrobacter rodentium
in Infected Mice
Authors: Vallance Bruce A. , Deng Wanyin , De Grado Myriam , Chan Crystal , Jacobson Kevan , Finlay B. Brett
Published: October 2002

Citrobacter rodentium
belongs to the attaching and effacing family of enteric bacterial pathogens that includes both enteropathogenic and enterohemorrhagic
Escherichia coli
. These bacteria infect their hosts by colonizing the intestinal mucosal surface and intimately attaching to underlying epithelial cells. The abilities of these pathogens to exploit the cytoskeleton and signaling pathways of host cells are well documented, but their interactions with the host's antimicrobial defenses, such as inducible nitric oxide synthase (iNOS), are poorly understood. To address this issue, we infected mice with
C. rodentium
and found that iNOS mRNA expression in the colon significantly increased during infection. Immunostaining identified epithelial cells as the major source for immunoreactive iNOS. Finding that nitric oxide (NO) donors were bacteriostatic for
C. rodentium
in vitro, we examined whether iNOS expression contributed to host defense by infecting iNOS-deficient mice. Loss of iNOS expression caused a small but significant delay in bacterial clearance without affecting tissue pathology. Finally, immunofluorescence staining was used to determine if iNOS expression was localized to infected cells by staining for the
C. rodentium
virulence factor, translocated intimin receptor (Tir), as well as iNOS. Interestingly, while more than 85% of uninfected epithelial cells expressed iNOS, fewer than 15% of infected (Tir-positive) cells expressed detectable iNOS. These results demonstrate that both iNOS and intestinal epithelial cells play an active role in host defense during
C. rodentium
infection. However, the selective expression of iNOS by uninfected but not infected cells suggests that this pathogen has developed mechanisms to locally limit its exposure to host-derived NO.
ATP and Control of Intracellular Growth of Mycobacteria by T Cells
Authors: Canaday David H. , Beigi Reza , Silver Richard F. , Harding Clifford V. , Boom W. Henry , Dubyak George R.
Published: October 2002

Extracellular ATP at millimolar concentrations inhibits growth of mycobacteria in human macrophages. Whether T cells can produce sufficient ATP is unknown. CD4+and CD8+T cells did not release sufficient ATP through either degranulation or lysis of bystander cells to restrict growth ofMycobacterium bovisBCG in monocytes.
Characterization and Immunogenicity of the CagF Protein of thecagPathogenicity Island ofHelicobacter pylori
Authors: Seydel Anke , Tasca Elisabetta , Berti Duccio , Rappuoli Rino , Del Giudice Giuseppe , Montecucco Cesare
Published: October 2002

Helicobacter pyloriinfection causes severe gastroduodenal diseases in humans. Its virulence is strongly increased by the presence of thecagpathogenicity island (cagPAI). It has been shown that CagA, a major antigen in humans, is translocated to the host cell via a secretion system encoded by thecagPAI. The roles of many of the proteins encoded within thecagPAI are not known. Here we report on the cloning and expression of CagF, one of those proteins. We show that CagF is associated to the outer membrane ofH. pyloriG27 and that the protein is always expressed with electrophoretic mobility variations among the 20 strains tested here. We have also found that natural infection withH. pyloriis able to induce antibodies against CagF.
Comparative Proteomic Analysis of Extracellular Proteins of
Edwardsiella tarda
Authors: Tan Y. P. , Lin Q. , Wang X. H. , Joshi S. , Hew C. L. , Leung K. Y.
Published: October 2002

A comparison of extracellular proteins of virulent and avirulent
Edwardsiella tarda
strains revealed several major, virulent-strain-specific proteins. Proteomic analysis identified two of the proteins in the virulent strain PPD130/91 as flagellin and SseB, which are virulence factors in bacterial pathogens. PCR amplification and DNA sequencing confirmed the presence of the genes that encode these proteins. Our results clearly demonstrated the potency of the proteomic approach in identifying virulence factors.
Opsonization of
Actinobacillus actinomycetemcomitans
by Immunoglobulin G Antibody Reactive with Phosphorylcholine
Authors: Purkall Donald , Tew John G. , Schenkein Harvey A.
Published: October 2002

We used two strains of
Actinobacillus actinomycetemcomitans
, one bearing phosphorylcholine (PC) (strain D045D-40) and one devoid of PC antigens (strain DB03A-42), as well as a nonencapsulated strain of
Streptococcus pneumoniae
(strain 39937), to examine the opsonic properties of physiological concentrations (⩽30 μg/ml) of purified human anti-PC immunoglobulin G (IgG). Anti-PC bound to both
A. actinomycetemcomitans
DO45D-40 and
S. pneumoniae
39937 and induced superoxide anion production by polymorphonuclear neutrophils; induction of the oxidative burst was inhibited by antibodies to either CD16 or CD32. Thus, anti-PC IgG at concentrations present in most human sera promotes the opsonization of PC-expressing strains of
A. actinomycetemcomitans
in the absence of complement, implying that anti-PC may be a protective antibody against such strains of bacteria.
Differences in Rate and Variability of Intracellular Growth of a Panel ofMycobacterium tuberculosisClinical Isolates within a Human Monocyte Model
Authors: Li Qing , Whalen Christopher C. , Albert Jeffrey M. , Larkin Rhonda , Zukowski Lynn , Cave M. Donald , Silver Richard F.
Published: October 2002

Significant differences were observed in the capacities ofMycobacterium tuberculosisclinical isolates to grow within human monocytes. Genotyping indicated that the four most rapidly growing isolates were members of the Beijing strain family.M. tuberculosisstrain H37Rv provided more reproducible infection than the clinical isolates orM. tuberculosisErdman.
Multiparameter Selection of
Helicobacter pylori
Antigens Identifies Two Novel Antigens with High Protective Efficacy
Authors: Sabarth N. , Hurwitz R. , Meyer T. F. , Bumann D.
Published: October 2002

A multiparameter selection of
Helicobacter pylori
antigens for vaccine development identified 15 candidates, 6 of which are known protective antigens. Two novel antigens with low homology to other organisms (HP0231 and HP0410) were overexpressed and purified with high yields. Both confer protective immunity in the mouse
Helicobacter
infection model.
Decreased Virulence of a Pneumolysin-Deficient Strain of
Streptococcus pneumoniae
in Murine Meningitis
Authors: Wellmer Andreas , Zysk Gregor , Gerber Joachim , Kunst Tammo , von Mering Matthias , Bunkowski Stefanie , Eiffert Helmut , Nau Roland
Published: October 2002

Pneumolysin, neuraminidases A and B, and hyaluronidase are virulence factors of
Streptococcus pneumoniae
that appear to be involved in the pathogenesis of meningitis. In a murine model of meningitis after intracerebral infection using mutants of
S. pneumoniae
D39, only mice infected with a pneumolysin-deficient strain were healthier at 32 and 36 h, had lower bacterial titers in blood at 36 h, and survived longer than the D39 parent strain. Cerebellar and spleen bacterial titers, meningeal inflammation, and neuronal damage scores remained uninfluenced by the lack of any of the virulence factors.
COOPERATIVE EFFECTS ON OPTICAL FORCES — DICKE'S BULLET
Authors: PANAT P. V. , LAWANDE S. V.
Published: October 2002

We investigate the cooperative effects on optical forces in a system of N two level atoms confined to a volume of dimension less than λ3, where λ is radiation wavelength and driven by a coherent radiation field with a spatial profile like Laguerre–Gaussian or ideal Bessel beam. We show a dramatic enhancement on optical forces as well as on the angular momentum imparted to the atom by a factor of N2.
APPLICATION OF THE EAM POTENTIALS TO THE STUDY OF DIFFUSION COEFFICIENTS OF LIQUID NOBLE AND TRANSITION METALS
Authors: ZIAUDDIN AHMED A. Z. , BHUIYAN G. M.
Published: October 2002

The embedded atom method (EAM) potentials, originally proposed for solid state calculations, have been applied to investigate the atomic transport property namely the diffusion coefficients of liquid Ni, Cu, Ag and Au. Two different liquid state theories, specifically the linearized Weeks–Chandler–Andersen (LWCA) theory and the Gibbs–Boguliubov variational method (GB) are used to evaluate the packing fraction near melting temperature. Calculated values for the diffusion coefficients are compared with the available experimental data. Results of variational calculations are found to be better in agreement. Results of calculations also allow us to conclude that the concerning EAM potentials are transferable to the study of atomic transport properties of liquid transition and noble metals.
THE FERMIONIC GREEN'S FUNCTION THEORY FOR CALCULATION OF MAGNETIZATION
Authors: WANG HUAI-YU , CHEN KE-QIU , WANG EN-GE
Published: October 2002

The fermionic Green's function theory of Heisenberg-like Hamiltonian is presented in this paper. For the case that the Hamiltonian is isotropic and the higher-order Green's function is asymmetrically decoupled, the present theory is equivalent to the bosonic Green's function theory. When the Hamiltonian is anisotropic and the higher-order Green's function is symmetrically decoupled, it gives the universal formula to calculate the three components of statistical average of spin operators which one encountered when dealing with ferromagnetic or ferroelectric systems described by anisotropic Heisenberg model or pseudospin model respectively. Both cases of  ≠ 0 and  = 0 are investigated. Explicit expressions are derived for spin value S = 1/2, 1, 3/2, 2, and 5/2. General expressions for any S value are suggested.
GEOMETRIC TRANSFORMATIONS AND NCCS THEORY IN THE LOWEST LANDAU LEVEL
Authors: ELIASHVILI M. , TSITSISHVILI G.
Published: October 2002

Chern-Simons type gauge field is generated by the means of singular area preserving transformations in the lowest Landau level of electrons forming fractional quantum Hall state. Dynamics is governed by the system of constraints which correspond to the Gauss law in the non-commutative Chern-Simons gauge theory and to the lowest Landau level condition in the picture of composite fermions. Physically reasonable solution to this constraints corresponds to the Laughlin state. It is argued that the model leads to the non-commutative Chern-Simons theory of the QHE and composite fermions.
SECOND-ORDER INTERFACE EQUATIONS FOR NONLINEAR DIFFUSION WITH VERY STRONG ABSORPTION
Authors: GALAKTIONOV VICTOR A. , SHMAREV SERGEI I. , VAZQUEZ JUAN L.
Published: October 2002

We derive the interface equations for weak (or maximal) nonnegative solutions u(x,t) of the porous medium equation with strong absorption in one dimension [Formula: see text] We consider here the very singular range where the exponents m > 1 and p < 1 satisfy 0 < m + p < 2. Unlike the range m + p≥2, where we have shown that the movement of the interface x =η(t) is described by a first-order equation, we prove that in this case there is actually a system of two equations: (i) a universal law N1(u(·,t))=a0, where a0=a0(m,p) is a fixed constant and N1(u)=(u(m - p)/2)x calculated at the interface (again a first-order operator), and (ii) a specific movement law, D+η(t) = N2(u(·,t)), where N2 is of the second order and D+η(t) is the right-hand derivative. We establish the instantaneous smoothing effect and prove optimal gradient bounds on the solutions as well as the second-order estimate on the interface. The analysis is based on intersection comparison with the set of the travelling wave solutions. The results apply to the linear diffusion m=1 with p∈(-1,1) and for fast diffusion, m∈(0,1), when p∈(-m,m). They can be also applied to equations of diffusion-convection type.
DUALITY IN INFINITE DIMENSIONAL FOCK REPRESENTATIONS
Authors: WANG WEIQIANG
Published: October 2002

We construct and study in detail various dual pairs acting on some infinite dimensional Fock representations between a finite dimensional classical Lie group and a completed infinite rank affine algebra associated to an infinite affine Cartan matrix. We give explicit decompositions of a Fock representation into a direct sum of irreducible isotypic subspaces with respect to the action of a dual pair, present explicit formulas for the highest weight vectors and calculate the corresponding highest weights. We further outline applications of these dual pairs to the study of tensor products of modules of such an infinite dimensional Lie algebra.
LOCAL MINIMIZERS FOR THE GINZBURG–LANDAU ENERGY NEAR CRITICAL MAGNETIC FIELD: PART I
Authors: SERFATY SYLVIA
Published: October 2002

We find local minimizers of the two-dimensional Ginzburg–Landau functionals depending on a large parameter κ, which describe the behavior of a superconductor in a prescribed exterior magnetic field hex. We prove an estimate on the critical value Hc1 of hex(κ), corresponding to the first phase-transition in which vortices appear in the superconductor; and we locate these vortices.
ON HYPERELLIPTIC C∞–LEFSCHETZ FIBRATIONS OF FOUR-MANIFOLDS
Authors: SIEBERT BERND , TIAN GANG
Published: October 2002

We show that hyperelliptic symplectic Lefschetz fibrations are symplectically birational to two-fold covers of rational ruled surfaces, branched in a symplectically embedded surface. This reduces the classification of genus 2 fibrations to the classification of certain symplectic submanifolds in rational ruled surfaces.
RESONANCE RELATIONS FOR SOLUTIONS OF THE ELLIPTIC QKZB EQUATIONS, FUSION RULES, AND EIGENVECTORS OF TRANSFER MATRICES OF RESTRICTED INTERACTION-ROUND-A-FACE MODELS
Authors: FELDER G. , VARCHENKO A.
Published: October 2002

Conformal blocks for the WZW model on tori can be represented by vector valued Weyl anti-symmetric theta functions on the Cartan subalgebra satisfying vanishing conditions on root hyperplanes. We introduce a quantum version of these vanishing conditions in the sl2 case. They are compatible with the qKZB equations and are obeyed by the hypergeometric solutions as well as by their critical level counterpart, which are Bethe eigenfunctions of IRF row-to-row transfer matrices. In the language of IRF models the vanishing conditions turn out to be equivalent to the sl2 fusion rules defining restricted models.
Aortic Pulse-Wave Velocity and Its Relationship to Mortality in Diabetes and Glucose Intolerance
Authors: Cruickshank Kennedy , Riste Lisa , Anderson Simon G. , Wright John S. , Dunn Graham , Gosling Ray G.
Published: October 2002

Background—

Arterial distensibility measures, generally from pulse-wave velocity (PWV), are widely used with little knowledge of relationships to patient outcome. We tested whether aortic PWV predicts cardiovascular and all-cause mortality in type 2 diabetes and glucose-tolerance–tested (GTT) multiethnic population samples.

Methods and Results—

Participants were randomly sampled from (1) a type 2 diabetes outpatient clinic and (2) primary care population registers, from which nondiabetic control subjects were given a GTT. Brachial blood pressures and Doppler-derived aortic PWV were measured. Mortality data over 10 years’ follow-up were obtained. At any level of systolic blood pressure (SBP), aortic PWV was greater in subjects with diabetes than in controls. Mortality risk doubled in subjects with diabetes (hazard ratio 2.34, 95% CI 1.5 to 3.74) and in those with glucose intolerance (2.12, 95% CI 1.11 to 4.0) compared with controls. For all groups combined, age, sex, and SBP predicted mortality; the addition of PWV independently predicted all-cause and cardiovascular mortality (hazard ratio 1.08, 95% CI 1.03 to 1.14 for each 1 m/s increase) but displaced SBP. Glucose tolerance status and smoking were other independent contributors, with African-Caribbeans experiencing reduced mortality risk (hazard ratio 0.41, 95% CI 0.25 to 0.69).

Conclusions—

Aortic PWV is a powerful independent predictor of mortality in both diabetes and GTT population samples. In displacing SBP as a prognostic factor, aortic PWV is probably further along the causal pathway for arterial disease and may represent a useful integrated index of vascular status and hence cardiovascular risk.
Associations of Extracranial Carotid Atherosclerosis Progression With Coronary Status and Risk Factors in Patients With and Without Coronary Artery Disease
Authors: Crouse John R. , Tang Rong , Espeland Mark A. , Terry James G. , Morgan Timothy , Mercuri Michele
Published: October 2002

Background—

Intimal medial thickness of the extracranial carotid arteries (IMT) is related to coronary artery disease (CAD) and CAD risk factors. Few studies have explored the association of risk factors with progression of IMT, and none have evaluated their associations with IMT progression specifically in patients with and without CAD.

Methods and Results—

We used coronary angiography to identify 280 patients equally divided between men and women and those with either ≥50% coronary artery stenosis or no CAD. Risk factors were measured at baseline and IMT was measured at baseline and yearly for 3 years in 241 of these individuals. Baseline risk factors and CAD status were related to IMT progression. IMT of patients with CAD progressed 3 times faster than that of patients with no CAD (mean±SEM, 33.7±7.4 versus 8.9±7.1 μm/year;
P
=0.02), and CAD status and high-density lipoprotein (HDL) cholesterol were independently associated with IMT progression. Male sex, increased waist to hip ratio, cigarette smoking, increased triglycerides, and decreased HDL cholesterol were associated with increased progression in CAD patients.

Conclusions—

Patients with CAD have more rapid progression of IMT than CAD-free controls, and risk factors are related to progression in them.
Hydroxymethylglutaryl Coenzyme A Reductase Inhibitor Simvastatin Prevents Cardiac Hypertrophy Induced by Pressure Overload and Inhibits p21
ras
Activation
Authors: Indolfi Ciro , Di Lorenzo Emilio , Perrino Cinzia , Stingone Angela Maria , Curcio Antonio , Torella Daniele , Cittadini Antonello , Cardone Luca , Coppola Carmela , Cavuto Luigi , Arcucci Oreste , Sacca Luigi , Avvedimento Enrico Vittorio , Chiariello Massimo
Published: October 2002

Background—

Patients with cardiac hypertrophy are at increased cardiovascular risk. It has been hypothesized that hydroxymethylglutaryl coenzyme A reductase inhibitors may exert beneficial effects other than their cholesterol-lowering actions. The aims of the study were to assess the in vivo effects of simvastatin (SIM) on cardiac hypertrophy and on
Ras
signaling in rats with ascending aorta banding.

Methods and Results—

Wistar rats were randomized to receive either treatment with SIM or placebo, and then short-term (group I) and long-term (group II) left ventricular pressure overload was performed by placing a tantalum clip on ascending aorta. At the end of treatment period, left and right ventricular weight, body weight, and tibial length were measured and echocardiographic evaluations were performed.
Ras
signaling was investigated by analyzing
Ras
membrane localization and activation,
ERK2
phosphorylation, and p27
kip1
and cdk4 levels. In SIM-treated rats, a significant reduction of left ventricular weight/body weight, echocardiographic left ventricular mass, and left ventricular end-diastolic diameter and end-diastolic pressure was found. In rats with pressure overload, SIM treatment significantly reduced
Ras
membrane targeting,
Ras
in vivo activation,
ERK2
phosphorylation, and the ratio cdk4/p27
kip1
.

Conclusions—

HMG CoA inhibitor SIM inhibits in vivo
Ras
signaling and prevents left ventricular hypertrophy development in aortic-banded animals.
Atrial Amyloidosis
Authors: Röcken Christoph , Peters Brigitte , Juenemann Gina , Saeger Wolfgang , Klein Helmut U. , Huth Christof , Roessner Albert , Goette Andreas
Published: October 2002

Background—

Structural changes, like atrial fibrosis, may increase the likelihood of atrial fibrillation (AF) occurring in response to triggering events. The influence of isolated atrial amyloidosis (IAA) is largely unknown.

Methods and Results—

Right atrial appendages (1 or 2 entire cross sections) were obtained from 245 patients undergoing open-heart surgery. Atrial amyloid was identified by Congo red staining and classified by immunohistochemistry. Amyloid was found in 40 (16.3%) of 245 patients, and all deposits were immunoreactive for atrial natriuretic peptide (ANP). Thirty-eight (15.5%) patients suffered from persistent AF. The presence of amyloid correlated with age and P-wave duration and was related to sex, valve diseases, and the presence of AF (
P
<0.01). The association between atrial amyloid, AF, and P-wave duration was independent of age and sex. According to multiple logistic regression analysis, amyloid was the only age- and sex-independent predictor for the presence of AF. Atrial fibrosis was not a predictor for AF, and the amount of amyloid correlated inversely with the degree of interstitial fibrosis (
P
=0.001;
r
=−0.55).

Conclusions—

Our study provides evidence that IAA affects atrial conduction and increases the risk of AF. The occurrence of IAA depends on age leading to the formation of an amyloid nidus. The progression and consequences of IAA are then influenced by pathological conditions, such as valve diseases, that increase synthesis and secretion of ANP. The inverse correlation between IAA and atrial fibrosis suggests that these patients may not benefit from treatment with ACE inhibitors to reduce the amount of atrial fibrosis.
Sequential Versus Simultaneous Biventricular Resynchronization for Severe Heart Failure
Authors: Sogaard Peter , Egeblad Henrik , Pedersen Anders K. , Kim Won Yong , Kristensen Bent Ø. , Hansen Peter S. , Mortensen Peter T.
Published: October 2002

Background—

Cardiac resynchronization therapy (CRT) by means of simultaneous biventricular pacing improves left ventricular systolic performance and synchrony in patients with heart failure and bundle-branch block. We used tissue tracking and 3D echocardiography to evaluate the impact of sequential CRT with individualized interventricular delay programming.

Methods and Results—

Twenty consecutive patients with severe heart failure and left bundle-branch block were included. Tissue tracking and 3D echocardiography were carried out before and on the day after pacemaker implantation. Eleven different interventricular delays were examined in each patient. Patients were reexamined after 3 months. Simultaneous CRT immediately reduced the extent of myocardium displaying delayed longitudinal contraction (DLC) from 48.6±16% to 23.2±13% (
P
<0.01) and increased left ventricular ejection fraction percentage (LVEF%) from 22.4±6% to 29.7±5% (
P
<0.01). However, optimum sequential CRT caused a further reduction in the extent of DLC from 23.2±13% to 11.1±7.2% (
P
<0.01), with a simultaneous increase in LVEF% (from 29.7±5% to 33.9±6%,
P
<0.01). Three months of optimum sequential CRT further improved LVEF% (from 33.6±6% to 38.6±7.2%,
P
<0.01). Tissue tracking detected the segments with DLC, and their location determined optimum interventricular delay programming. Compared with simultaneous CRT, sequential CRT increased diastolic filling time by 7±2.5%.

Conclusions—

Compared with simultaneous CRT, sequential CRT significantly improves left ventricular systolic and diastolic performance. Tissue tracking can be used to select optimum interventricular delay during CRT.
THE BOOK OF RUTH AND THE LOVE OF THE LAND
Authors: Ostriker Alicia
Published: October 2002

The book of Ruth may be read as a countertext, that is a text embedded within the scriptural text that forms a counter-current to its prevailing concepts or motifs, thereby enriching the Scripture as a whole. Ruth deviates from dominant biblical norms in four interlocking ways, producing a radical vision while remaining seamlessly attached to the prevailing traditions that it implicitly transforms. It is essentially a pastoral idyll yet it is woven into the history of Israel. It is strongly gynocentric, though framed by an androcentric closure. It represents God as uniquely associated with fertility and invokes the presence of God primarily through the chesed, kindness, of the story's characters. Lastly, the treatment of land and of boundaries between lands, in Ruth, does not entail conquest. Elsewhere in biblical narrative, land is associated with nation and empire; here it is associated with fertility and benevolence. Ostensibly taking place during the time of the Judges, the book of Ruth is a virtual antidote to its sagas of slaughter. It is a story about the possibilities of peace.
Visualising microglial activation in vivo
Authors: Banati Richard B.
Published: October 2002

In health, microglia reside as quiescent guardian cells ubiquitously, but isolated without any cell‐cell contacts amongst themselves, throughout the normal CNS. In disease, however, they act as swift “sensors” for pathological events, including subtle ones without any obvious structural damage. Once activated, microglia show a territorially highly restricted involvement in the disease process. This property, peculiar to microglia, confers to them diagnostic value for the accurate spatial localisation of any active disease process, acute or chronic. In the brain, the isoquinoline PK11195, a ligand for the peripheral benzodiazepine binding site (PBBS), binds with relative cellular selectivity to activated, but not resting, microglia. Labelled with carbon‐11, (R)‐PK11195 and positron emission tomography (PET) have been used for the study of inflammatory and neurodegenerative brain disease in vivo. These studies demonstrate meaningfully distributed patterns of regional [11C](R)‐PK11195 signal increases that correlate with clinically observed loss of function. Increased [11C](R)‐PK11195 binding closely mirrors the histologically well‐described activation of microglia in the penumbra of focal lesions, as well as in the distant, anterograde, and retrograde projection areas of the lesioned neural pathway. There is also some indication that in long‐standing alterations of a neural network with persistent abnormal input, additional signals of glial activation may also emerge in transsynaptic areas. These data suggest that the injured brain is less static than commonly thought and shows subtle glial responses even in macroanatomically stable appearing regions. This implies that glial activation is not solely a sign of tissue destruction, but possibly of disease‐induced adaptation or plasticity as well. Whilst further technological and methodological advances are necessary to achieve routine clinical value and feasibility, a systematic attempt to image glial cells in vivo is likely to furnish valuable information on the cellular pathology of CNS diseases and their progression within the distributed neural architecture of the brain. GLIA 40:206–217, 2002. © 2002 Wiley‐Liss, Inc.
Microglia in brain tumors
Authors: Graeber Manuel B. , Scheithauer Bernd W. , Kreutzberg Georg W.
Published: October 2002

Microglia have long been ignored by neurooncologists. This has changed with the realization that microglial cells not only occur within and around brain tumors but also contribute significantly to the actual tumor mass, notably in astrocytic gliomas. In addition, it has been speculated that microglia could play a role in the defense against neoplasms of the nervous system. However, the biological success of these tumors, i.e., their highly malignant behavior, indicates that natural microglial defense mechanisms do not function properly in astrocytomas. In fact, there is evidence that microglial behavior is controlled by tumor cells, supporting their growth and infiltration. This unexpected “Achilles heel” of microglial immune defense illustrates the risk of generalizing on the basis of a single aspect of microglial biology. Microglia are highly plastic cells, capable of exerting cytotoxic functions under conditions of CNS infections, but not necessarily during glioma progression. Thus, the suggestion that microglial activation through stimulation by cytokines (e.g., interferon‐γ) will benefit patients with brain tumors could prove fatally wrong. Therapeutic recruitment of microglia to treat such diffusely infiltrative brain tumors as astrocytic gliomas must be considered premature. GLIA 40:252–259, 2002. © 2002 Wiley‐Liss, Inc.
Scavenger receptors in neurobiology and neuropathology: Their role on microglia and other cells of the nervous system
Authors: Husemann Jens , Loike John D. , Anankov Roman , Febbraio Maria , Silverstein Samuel C.
Published: October 2002

Scavenger receptor class A (SR‐A, CD204), scavenger receptor‐BI (SR‐BI), and CD36 are cell surface proteins that mediate cell adhesion to, and endocytosis of, various native and pathologically modified substances, and participate in intracellular signaling, lipid metabolism, and host defense against bacterial pathogens. Microglia, Mato cells, astrocytes, cerebral microvascular endothelial cells, cerebral arterial smooth muscle cells, and retinal pigment epithelial cells express one or more of these SR. Expression of SR‐A and SR‐BI by microglia is developmentally regulated. Neonatal microglia express SR‐A and SR‐BI, while microglia in normal mouse and human adult brain express neither. Astrocytes in adult brain express SR‐BI. In Alzheimer's disease, microglial expression of SR‐A is increased. Such findings, and evidence that SR‐A and SR‐BI mediate adhesion and endocytosis of fibrillar β‐amyloid by microglia and astrocytes, respectively, and that SR‐A, SR‐BI, and CD36 participate in secretion of reactive oxygen species by microglia, suggest roles for these receptors in homeostasis and neuropathology. GLIA 40:195–205, 2002. © 2002 Wiley‐Liss, Inc.
Microglia as neuroprotective, immunocompetent cells of the CNS
Authors: Streit Wolfgang J.
Published: October 2002

The role of glial cells is to support and sustain proper neuronal function and microglia are no exception to this. This viewpoint article emphasizes the fundamental interdependence of microglia and neurons and takes a look at the possibility of what could happen if microglial cells became dysfunctional as a result of aging, genetics, or epigenetics. Could microglial senescence be a factor in the pathogenesis of Alzheimer's and other neurodegenerative diseases? The cautious answer to that question is ‘yes’. Future studies along these lines may provide novel insights into microglial involvement in neurodegenerative disease pathogenesis. GLIA 40:133–139, 2002. © 2002 Wiley‐Liss, Inc.
An empirical analysis of the impact of stock index futures trading on securities dealers' inventory risk in the NASDAQ market
Authors: Sarkar Salil K. , Tripathy Niranjan
Published: October 2002

Stock index futures contracts (SIFCs) were developed in part to allow equity investors to conveniently hedge portfolio risks. Therefore, we may expect to observe smaller bid/ask spreads among NASDAQ equities following the introduction of trading in SIFCs. The potential transactions cost reduction results from the enhanced ability of dealers to hedge their inventory risk. Accordingly, we analyze the daily returns and bid/ask spreads of all CRSP‐listed NASDAQ stocks for a 10‐year period surrounding the introduction of three SIFCs in order to determine whether the introduction of these contracts has affected transactions costs in the NASDAQ equity market. Our results indicate that bid/ask spreads narrowed significantly following the introduction of stock index futures trading. Moreover, the behavior of the spreads leads us to the conclusion that risk reduction through cost‐effective hedging via stock index futures trading may have been the cause.