bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Membrane Budding as an Alternative Release Mechanism of the Extracellular Enveloped Form of Vaccinia Virus from HeLa Cells
Authors: Meiser Andrea , Sancho Carmen , Krijnse Locker Jacomine
Published: August 2003

In HeLa cells the assembly of modified vaccinia virus Ankara (MVA), an attenuated vaccinia virus (VV) strain, is blocked. No intracellular mature viruses (IMVs) are made and instead, immature viruses accumulate, some of which undergo condensation and are released from the cell. The condensed particles may undergo wrapping by membranes of the trans-Golgi network and fusion with the plasma membrane prior to their release (M. W. Carroll and B. Moss, Virology 238:198-211, 1997). The present study shows by electron microscopy (EM), however, that the dense particles made in HeLa cells are also released by a budding process at the plasma membrane. By labeling the plasma membrane with antibodies to B5R, a membrane protein of the extracellular enveloped virus, we show that budding occurs at sites that concentrate this protein. EM quantitation revealed that the cell surface around a budding profile was as strongly labeled with anti-B5R antibody as were the extracellular particles, whereas the remainder of the plasma membrane was significantly less labeled. To test whether budding was a characteristic of MVA infection, HeLa cells were infected with the replication competent VV strains Western Reserve strain (WR) and International Health Department strain-J (IHD-J) and also prepared for EM. EM analyses, surprisingly, revealed for both virus strains IMVs that evidently budded at the cell surface at sites that were significantly labeled with anti-B5R. EM also indicated that budding of MVA dense particles was more efficient than budding of IMVs from WR- or IHD-J-infected cells. This was confirmed by semipurifying [
35
S]methionine-labeled dense particles or extracellular enveloped virus (EEVs) from the culture supernatant of MVA- or IHD-J-infected HeLa cells, respectively, showing that threefold more labeled dense particles were secreted than EEVs. Finally, although the released MVA dense particles contain some DNA, they are not infectious, as assessed by plaque assays.
Efficient Isolation of Wild Strains of Canine Distemper Virus in Vero Cells Expressing Canine SLAM (CD150) and Their Adaptability to Marmoset B95a Cells
Authors: Seki Fumio , Ono Nobuyuki , Yamaguchi Ryoji , Yanagi Yusuke
Published: August 2003

We have previously shown that canine signaling lymphocyte activation molecule (SLAM; also known as CD150) acts as a cellular receptor for canine distemper virus (CDV). In this study, we established Vero cells stably expressing canine SLAM (Vero.DogSLAMtag cells). Viruses were isolated in Vero.DogSLAMtag cells one day after inoculation with spleen samples from five out of seven dogs with distemper. By contrast, virus isolation with reportedly sensitive marmoset B95a cells was only successful from three diseased animals at 7 to 10 days after inoculation, and no virus was recovered from any dogs when Vero cells were used for isolation. The CDV strain isolated in Vero.DogSLAMtag cells did not cause cytopathic effects in B95a and human SLAM-expressing Vero cells, whereas the strain isolated in B95a cells from the same dog did so in canine or human SLAM-expressing Vero cells as well as B95a cells. There were two amino acid differences in the hemagglutinin sequence between these strains. Cell fusion analysis after expression of envelope proteins and vesicular stomatitis virus pseudotype assay showed that their hemagglutinins were responsible for the difference in cell tropism between them. Site-directed mutagenesis indicated that glutamic acid to lysine substitution at position 530 of the hemagglutinin was required for the adaptation to the usage of marmoset SLAM. Our results indicate that Vero cells stably expressing canine SLAM are highly sensitive to CDV in clinical specimens and that only a single amino acid substitution in the hemagglutinin can allow the virus to adapt to marmoset SLAM.
Transformation of Mouse Fibroblasts by Jaagsiekte Sheep Retrovirus Envelope Does Not Require Phosphatidylinositol 3-Kinase
Authors: Maeda Naoyoshi , Inoshima Yasuo , Fruman David A. , Brachmann Saskia M. , Fan Hung
Published: August 2003

Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma, a transmissible lung cancer of sheep. The envelope of JSRV may have oncogenic properties, since it can morphologically transform mouse NIH 3T3 cells and other fibroblast lines. Recently, we found that the cytoplasmic tail of the envelope transmembrane (TM) protein is necessary for transformation, and in particular a consensus binding motif (YXXM) for phosphatidylinositol 3-kinase (PI3K) is important. Moreover, JSRV-transformed cells show phosphorylation (activation) of Akt/protein kinase B, a downstream target of PI3K. In these studies, we directly tested for the involvement of PI3K in transformation by JSRV. Contrary to expectations, four different experiments indicated that PI3K is not necessary for JSRV-induced transformation: (i) cotransfection with a dominant negative truncated form of the PI3K regulatory subunit (Δp85) did not affect transformation frequency, (ii) cells stably expressing Δp85 showed the same frequencies of transformation as parental NIH 3T3 cells, (iii) fibroblasts established from double-knockout mice lacking PI3K p85α and p85β could be transformed with JSRV envelope, and (iv) incubation of cells with the PI3K inhibitor LY294002 did not specifically inhibit transformation, nor did the drug reverse transformation of JSRV-transformed cells. One alternate explanation for the lack of transformation by YXXM mutants could be that they were defective in intracellular trafficking. However, confocal microscopy of epitope-tagged envelope proteins of both wild-type and nontransforming YXXM mutants showed a cell surface or plasma membrane localization. While PI3K is not required for JSRV-induced transformation of NIH 3T3 cells, the downstream target Akt kinase was found to be activated (phosphorylated) in JSRV-transformed PI3K-negative cells. Therefore, JSRV envelope can induce PI3K-independent phosphorylation of Akt.
Vaccinia Virus Interleukin-18-Binding Protein Promotes Virulence by Reducing Gamma Interferon Production and Natural Killer and T-Cell Activity
Authors: Reading Patrick C. , Smith Geoffrey L.
Published: August 2003

Interleukin-18 (IL-18) is a proinflammatory cytokine that promotes natural killer (NK) and T-cell activation. Several poxviruses, including vaccinia virus (VV), encode a soluble IL-18-binding protein (IL-18bp). The role of the VV IL-18bp (gene C12L) in vivo was studied with wild-type (vC12L), deletion mutant (vΔC12L), and revertant (vC12L-rev) viruses in a murine intranasal model of infection. The data show that vΔC12L was markedly attenuated, characterized by a mild weight loss and reduced virus titers in lungs, brain, and spleen. Three days after infection, NK cytotoxic activity was augmented in the lung, spleen, and mediastinal lymph nodes (MLNs) of vΔC12L-infected mice compared to controls. Seven days after infection, vΔC12L-infected mice displayed heightened VV-specific cytotoxic T-lymphocyte (CTL) responses in the lungs, spleen, and MLNs. Gamma interferon (IFN-γ) levels were also dramatically elevated in lavage fluids and cells from lungs of mice infected with vΔC12L. Finally, we demonstrate that IL-18 is produced in vitro and in vivo after VV infection. Taken together, these data demonstrate a role for the vIL-18bp in counteracting IL-18 in both the innate and the specific immune response to VV infection and indicate that the ability of IL-18 to promote vigorous T-cell responses (cytotoxic activity and IFN-γ production) is a critical factor in the accelerated clearance of the vΔC12L mutant.
Integrin-Using Rotaviruses Bind α2β1 Integrin α2 I Domain via VP4 DGE Sequence and Recognize αXβ2 and αVβ3 by Using VP7 during Cell Entry
Authors: Graham Kate L. , Halasz Peter , Tan Yan , Hewish Marilyn J. , Takada Yoshikazu , Mackow Erich R. , Robinson Martyn K. , Coulson Barbara S.
Published: August 2003

Integrins α2β1, αXβ2, and αVβ3 have been implicated in rotavirus cell attachment and entry. The virus spike protein VP4 contains the α2β1 ligand sequence DGE at amino acid positions 308 to 310, and the outer capsid protein VP7 contains the αXβ2 ligand sequence GPR. To determine the viral proteins and sequences involved and to define the roles of α2β1, αXβ2, and αVβ3, we analyzed the ability of rotaviruses and their reassortants to use these integrins for cell binding and infection and the effect of peptides DGEA and GPRP on these events. Many laboratory-adapted human, monkey, and bovine viruses used integrins, whereas all porcine viruses were integrin independent. The integrin-using rotavirus strains each interacted with all three integrins. Integrin usage related to VP4 serotype independently of sialic acid usage. Analysis of rotavirus reassortants and assays of virus binding and infectivity in integrin-transfected cells showed that VP4 bound α2β1, and VP7 interacted with αXβ2 and αVβ3 at a postbinding stage. DGEA inhibited rotavirus binding to α2β1 and infectivity, whereas GPRP binding to αXβ2 inhibited infectivity but not binding. The truncated VP5* subunit of VP4, expressed as a glutathione
S
-transferase fusion protein, bound the expressed α2 I domain. Alanine mutagenesis of D308 and G309 in VP5* eliminated VP5* binding to the α2 I domain. In a novel process, integrin-using viruses bind the α2 I domain of α2β1 via DGE in VP4 and interact with αXβ2 (via GPR) and αVβ3 by using VP7 to facilitate cell entry and infection.
cis
-Acting Elements Required for Efficient Packaging of Brome Mosaic Virus RNA3 in Barley Protoplasts
Authors: Asmira Damayanti Tri , Tsukaguchi Satoshi , Mise Kazuyuki , Okuno Tetsuro
Published: August 2003

Brome mosaic virus (BMV) is a positive-sense RNA plant virus, the tripartite genomic RNAs of which are separately packaged into virions. RNA3 is copackaged with subgenomic RNA4. In barley protoplasts coinoculated with RNA1 and RNA2, an RNA3 mutant with a 69-nucleotide (nt) deletion in the 3′-proximal region of the 3a open reading frame (ORF) was very poorly packaged compared with other RNA3 mutants and wild-type RNA3, despite their comparable accumulation in the absence of coat protein. Computer analysis of RNA secondary structure predicted two stem-loop (SL) structures (i.e., SL-I and SL-II) in the 69-nt region. Disruption of SL-II, but not of SL-I, significantly reduced RNA3 packaging. A chimeric BMV RNA3 (B3Cmp), with the BMV 3a ORF replacing that of cucumber mosaic virus (CMV), was packaged negligibly, whereas RNA4 was packaged efficiently. Replacement of the 3′-proximal region of the CMV 3a ORF in B3Cmp with the 3′-proximal region of the BMV 3a ORF significantly improved packaging efficiency, and the disruption of SL-II in the substituted BMV 3a ORF region greatly reduced packaging efficiency. These results suggest that the 3′-proximal region of the BMV 3a ORF, especially SL-II predicted between nt 904 and 933, plays an important role in the packaging of BMV RNA3 in vivo. Furthermore, the efficient packaging of RNA4 without RNA3 in B3Cmp-infected cells implies the presence of an element in the 3a ORF of BMV RNA3 that regulates the copackaging of RNA3 and RNA4.
Nedd4 Regulates Egress of Ebola Virus-Like Particles from Host Cells
Authors: Yasuda Jiro , Nakao Mitsuyoshi , Kawaoka Yoshihiro , Shida Hisatoshi
Published: August 2003

Ebola virus budding is mediated by two proline-rich motifs, PPxY and PTAP, within the viral matrix protein VP40. We have previously shown that a Nedd4-like protein BUL1, but not Nedd4, positively regulates budding of type D retrovirus Mason-Pfizer monkey virus (J. Yasuda, E. Hunter, M. Nakao, and H. Shida, EMBO Rep. 3:636-640, 2002). Here, we report that the cellular E3 ubiquitin ligase Nedd4 regulates budding of VP40-induced virus-like particles (VLPs) through interaction with the PPxY motif. Mutation of the active site cysteine (C894A), resulting in abrogation of ubiquitin ligase activity, impaired the function of Nedd4 on budding. In addition, the WW domains of Nedd4 are essential for binding to the viral PPxY motif, and a small fragment of Nedd4 containing only WW domains significantly inhibited Ebola VLP budding in a dominant-negative manner. Our findings suggest that the viruses containing PPxY as an L-domain motif specifically use E3 in the process of virus budding. We also examined the effects of overexpression of Tsg101 and its mutant. As expected, Tsg101 enhanced VP40-induced VLP release, and TsgΔC, which lacks its C-terminal half, inhibited VLP release. These results indicate that Nedd4, together with Tsg101, plays an important role in Ebola virus budding.
Assorted Mutations in the Envelope Gene of Simian Immunodeficiency Virus Lead to Loss of Neutralization Resistance against Antibodies Representing a Broad Spectrum of Specificities
Authors: Johnson Welkin E. , Sanford Hannah , Schwall Linda , Burton Dennis R. , Parren Paul W. H. I. , Robinson James E. , Desrosiers Ronald C.
Published: August 2003

Simian immunodeficiency virus (SIV) of macaques isolate SIVmac239 is highly resistant to neutralization by polyclonal antisera or monoclonal antibodies, a property that it shares with most primary isolates of human immunodeficiency virus type 1 (HIV-1). This resistance is important for the ability of the virus to persist at high levels in vivo. To explore the physical features of the viral envelope complex that contribute to the neutralization-resistant phenotype, we examined a panel of SIVmac239 derivatives for sensitivity to neutralization by a large collection of monoclonal antibodies (MAbs). These MAbs recognize both linear and conformational epitopes throughout the viral envelope proteins. The variant viruses included three derivatives of SIVmac239 with substitutions in specific N-linked glycosylation sites of gp120 and a fourth variant that lacked the100 amino acids that encompass the V1 and V2 loops. Also included in this study was SIVmac316, a variant of SIVmac239 with distributed mutations in
env
that confer significantly increased replicative capacity in tissue macrophages. These viruses were chosen to represent a broad range of neutralization sensitivities based on susceptibility to pooled, SIV-positive plasma. All three of these very different kinds of mutations (amino acid substitutions, elimination of N-glycan attachment sites, and a 100-amino-acid deletion spanning variable loops V1 and V2) dramatically increased sensitivity to neutralization by MAbs from multiple competition groups. Thus, the mutations did not simply expose localized epitopes but rather conferred global increases in neutralization sensitivity. The removal of specific N-glycan attachment sites from V1 and V2 led to increased sensitivity to neutralization by antibodies recognizing epitopes from both within and outside of the V1-V2 sequence. Surprisingly, while most of the mutations that gave rise to increased sensitivity were located in the N-terminal half of gp120 (surface subunit [SU]), the greatest increases in sensitivity were to MAbs recognizing the C-terminal half of gp120 or the ectodomain of gp41 (transmembrane subunit [TM]). This reagent set and information should now be useful for defining the physical, structural, thermodynamic, and kinetic factors that influence relative sensitivity to antibody-mediated neutralization.
More on the Gauge-Fixed D3-Brane Action with Dilaton–Axion Coupling from N=1 Superspace
Authors: Ketov Sergei V.
Published: August 2003

The gauge-fixed action of a "spacetime-filling" D3-brane with dilaton–axion coupling is formulated in N=1 superspace. We investigate its symmetries by paying special attention to a possible nonlinearly realized extra supersymmetry, and emphasize the need of a linear superfield coupled to an Abelian Chern–Simons superfield to represent a dilaton–axion supermultiplet in the off-shell manifestly supersymmetric approach.
Missing Mass as Evidence for Modified Newtonian Dynamics at Low Accelerations
Authors: Sanders R. H.
Published: August 2003

Milgrom has proposed that the appearance of discrepancies between the Newtonian dynamical mass and the directly observable mass in astronomical systems could be due to a breakdown of Newtonian dynamics in the limit of low accelerations rather than the presence of unseen matter. Milgrom's hypothesis, modified Newtonian dynamics or MOND, has been remarkably successful in explaining systematic properties of spiral and elliptical galaxies and predicting in detail the observed rotation curves of spiral galaxies with only one additional parameter — a critical acceleration which is on the order of the cosmologically interesting value of cH0. Here we review the empirical successes of this idea and discuss its possible extension to cosmology and structure formation.
Proper Fluctuations Associated with Quantum Tunneling in Field Theory
Authors: Maziashvili Michael
Published: August 2003

It is shown that, to the lowest order in ℏ, the particle production related to the tunneling that leads to the false vacuum decay is described by the orthogonal part of fluctuation field with respect to the bounce solution. As a simple example the spatially homogeneous tunneling is considered in order to illustrate the consequences coming from such a restriction of the fluctuation field.
The Notion of N=1 Supergeometric Vertex Operator Superalgebra and the Isomorphism Theorem
Authors: Barron Katrina
Published: August 2003

We introduce the notion of N=1supergeometric vertex operator superalgebra motivated by the geometry underlying genus-zero, two-dimensional, holomorphic N=1 superconformal field theory. We then show, assuming the convergence of certain projective factors, that the category of such objects is isomorphic to the category of N=1 Neveu–Schwarz vertex operator superalgebras.
Regularity and Blow-Up Analysis for J-Holomorphic Maps
Authors: Wang Changyou
Published: August 2003

If u∈H1(M,N) is a weakly J-holomorphic map from a compact without boundary almost hermitian manifold (M,j,g) into another compact without boundary almost hermitian manifold (N,J,h). Then it is smooth near any point x where Du has vanishing Morrey norm ℳ2,2m-2, with 2m= dim (M). Hence H2m-2measure of the singular set for a stationary J-holomorphic map is zero. Blow-up analysis and the energy quantization theorem are established for stationary J-holomorphic maps. Connections between stationary J-holomorphic maps and stationary harmonic maps are given for either almost Kähler manifolds M and N or symmetric ∇hJ.
Invariants of Legendrian Knots in Circle Bundles
Authors: Sabloff Joshua M.
Published: August 2003

Let M be a circle bundle over a Riemann surface that supports a contact structure transverse to the fibers. This paper presents a combinatorial definition of a differential graded algebra (DGA) that is an invariant of Legendrian knots in M. The invariant generalizes Chekanov's combinatorial DGA invariant of Legendrian knots in the standard contact 3-space using ideas from Eliashberg, Givental, and Hofer's contact homology. The main difficulty lies in dealing with what are ostensibly 1-parameter families of generators for the DGA; these are solved using "Morse–Bott" techniques. As an application, the invariant is used to distinguish two Legendrian knots that are smoothly isotopic, realize a nontrivial homology class, but are not Legendrian isotopic.
Perturbations of the Harmonic Map Equation
Authors: Kappeler T. , Kuksin S. , Schroeder V.
Published: August 2003

We consider perturbations of the harmonic map equation in the case where the target manifold is a closed Riemannian manifold of nonpositive sectional curvature. For any semilinear and, under some extra conditions, quasilinear perturbation, the space of classical solutions within a homotopy class is proved to be compact. An important ingredient for our analysis is a new inequality for maps in a given homotopy class which can be viewed as a version of the Poincaré inequality for such maps.
Network Calculus-Based Delay Analysis for QoS Provision in Buffered Crossbar Switch
Authors: Duan Qiang , Li Xinghe , Zhang Linjie
Published: August 2003

The buffered crossbar switch employs crossbar-based switching fabric architecture with internal buffers and combined input and output queueing scheme. It is promising to achieve high performance without complex implementation. In this paper, we apply network calculus-based analytical technique to study the delay performance of the buffered crossbar switch. We set up a service curve-based model for the traffic control system of buffered crossbar switch. Based on this model, we develop techniques that can determine the end-to-end service curve guaranteed to a flow of traffic and calculate the packet delay upper bound of this flow. Then we analyze the determining factors of this delay bound performance and the relation between the delay bound and the amount of resources (bandwidth and credits) allocated in the switch to a flow.
A Media Access Control Protocol for Broadcast Type Super High-Speed WDM Networks
Authors: Koyama Akio , Akiyama Masato
Published: August 2003

In this paper, we propose a new media access protocol for single hop Wavelength Division Multiplexing (WDM) networks with a passive star topology. In the conventional protocols, when the control packets collided with other ones or the packets didn't get a data channel from the channel reservation mechanism, these packets should be retransmitted. But, when transmission distance becomes long, it takes a long time to transmit the control packets and the propogation dalay time will be long. We propose a new protocol that can allocate data channels without retransmitting control packets except the collided ones. By using the proposed protocol, it is possible to reduce the transmission delay time and to get high throughput because the number of retransmitted control packets is reduced. The simulation results show that the proposed protocol has good performance comparied with conventional protocols.
Performance Evaluation of Crossbar Switch Fabrics in Core Routers
Authors: Li Wenjie , Gong Yiping , Liu Bin
Published: August 2003

Many researchers have pointed out that using complex scheduling algorithms in input queuing switches with virtual output queuing (VOQ) scheme can achieve 100% throughput. But these algorithms are too complex to be implemented in hardware. In this paper, based on combined input/output queuing (CIOQ) switch fabrics, we propose a simple scheduling algorithm named outlet priority round robin (OPRR). For synthetic workloads we consider, including uniform and bursty traffic models, the performance of OPRR in VOQ mode and single queue mode is evaluated respectively. Through the simulation results we show that 1) OPRR algorithm, coupled with the speedup of 2, can lead to performance very close to output queuing switches, and 2) under the same condition, OPRR algorithm in single queue mode behaves almost identically to VOQ mode. These results are very useful to direct the design and implementation of switch fabrics in core routers.
On the Relative Performance Merits of Switching Techniques Under Bursty Loads
Authors: Min Geyong , Ould-Khaoua Mohamed , Mackenzie Lewis M.
Published: August 2003

Switching techniques have a strong effect on the performance of interconnection networks. Many studies have shown that traffic loads in parallel computation environments can exhibit burstiness property. In order to obtain a deep understanding of the efficiency of switching techniques, this study proposes an analytical performance model for pipelined circuit switching (PCS) in binary n-cube networks under bursty traffic, which is modeled by a switched Poisson process (SPP). Simulation experiments demonstrate that the proposed model exhibits a good degree of accuracy. This model and the one proposed in Ref. [13] for wormhole switching (WS) are then applied to investigate the relative performance merits of PCS and WS in the presence of bursty loads.
Video Presentation Recording and On-Line Broadcasting
Authors: Shih Timothy K. , Wang Ying-Hong , Liao Yi-Chun , Chuang Jung-Ken
Published: August 2003

Distance learning programs use on-line video records to deliver pre-recorded lectures. And, video communication systems can be used as a discussion tool. In this paper, we start our discussion on a multimedia presentation recording system which we had developed. We then present how the video recording concept can be further extended to realize an augmented video conferencing system, which can be used as a peer-to-peer discussion tool, as well as a lecture broadcasting system. We also point out that an object tracking technology can be further integrated to enhance the tool, to enable a more realistic and useful system for the discussion in distance education.
Notification-Based QOS Control Protocol for Group Communication
Authors: Tojo Takuya , Enokido Tomoya , Takizawa Makoto
Published: August 2003

This paper discusses a group communication protocol to exchange multimedia messages in a group of multiple peer processes. Quality of Service (QoS) required by an application has to be supported. In traditional protocols like RTP, a process can reliably deliver messages to one or more than one process. In the group communication, each process sends a message to multiple processes while receiving messages from multiple processes in a group. Due to the limited computation and communication capacity, we cannot adopt traditional one-to-one or one-to-many transmission ways to the group communication. We propose a notification-based data transmission procedure to exchange multimedia messages among multiple processes so as to satisfy QoS requirement.
An Efficient Algorithm for Solving the Minimum Blocking Frequency Assignment Problem Using Channel Reassignment
Authors: Ma Gary H. K. , Zomaya Albert Y.
Published: August 2003

The channel allocation problem (CAP) that involves the allocation a disjoint set of channels to meet the call demands for a cellular network is an NP-complete combinatorial optimisation problem [1]. The CAP can be viewed as: static (during the initial design/planning of the cellular network) and dynamic (when the network is operational). This paper presents a new algorithm designed to solve the online call control problem. This algorithm is a modified version of the maximum channel packing channel allocation (MCPCA) scheme, proposed by [19]. The original MCPCA scheme aims at maximising the reuse of channels (i.e. dense packing) and simulation results showed that it is more efficient than fixed channel assignment (FCA) or borrowing channel assignment (BCA) schemes for solving the class of minimum blocking frequency assignment problem (MB-FAP) [2]. The new algorithm, entitled maximum channel packing channel assignment with re-assignment (MCPCA-RA), takes the dense packing mechanism further by allowing a neighbouring cell to re-assigns a channel to an existing call and releases the channel previously used to the new request. Simulation results that the number of blocked calls is reduced by an average of 6% compared to the original MCPCA scheme, but at the cost of extra computations due to the reassignment mechanism. Since the reassignment computations only involve cells in the local neighbourhood and can be compute in a parallel manner, MCPCA-RA algorithm is practical and efficient in real-time.
Intelligence Chinese Document Semantic Indexing System
Authors: Shi Zhongzhi , He Qing , Jia Ziyan , Li Jiayou
Published: August 2003

With the rapid growth of the Internet, how to get information from this huge information space becomes an even more important problem. In this paper, An Intelligence Chinese Document Semantic Indexing System; ICDSIS, is proposed. Some new technologies are integrated in ICDSIS to obtain good performance. ICDSIS is composed of four key procedures. A parallel, distributed and configurable Spider is used for information gather; a multi-hierarchy document classification approach combining the information gain initially processes gathered web documents; a swarm intelligence based document clustering method is used for information organization; a concept-based retrieval interface is applied for user interactive retrieval. ICDSIS is an all-sided solution for information retrieval on the Internet.
Uterine Artery Structural and Functional Changes During Pregnancy in Tissue Kallikrein–Deficient Mice
Authors: Hilgers Rob H.P. , Bergaya Sonia , Schiffers Paul M.H. , Meneton Pierre , Boulanger Chantal M. , Henrion Daniel , Lévy Bernard I. , De Mey Jo G.R.
Published: August 2003

Objective—

Tissue kallikrein (TK) participates in acute flow-induced dilatation (FID) of large arteries. We investigated whether TK deficiency blunts FID and alters chronic flow-related arterial structural and functional changes in resistance-sized muscular arteries.

Methods and Results—

Vasomotor responses and structural parameters were determined in uterine arteries isolated from nonpregnant, 18- to 19-day pregnant, and 7-day postpartum TK
−/−
and TK
+/+
littermate mice. In TK
−/−
mice, values of diameter, medial cross-sectional area (CSA), myogenic tone, and dilatation in response to acetylcholine were comparable to those values in TK
+/+
mice, but FID (0 to 100 μL/min) was significantly reduced (55±4% versus 85±4% in TK
+/+
mice). In both mouse strains, pregnancy resulted in significant increases in diameter and medial CSA and in the
N
w
-nitro-
l
-arginine methyl ester–sensitive component of FID. By 7 days after pregnancy, uterine arterial diameter and CSA values no longer differed from nonpregnant values, and FID was markedly reduced in TK
−/−
and TK
+/+
mice.

Conclusions—

These observations (1) confirm at the level of resistance arteries the key role of TK in FID and (2) indicate that TK deficiency does not compromise arterial remodeling and changes in the contribution of NO to FID during and after pregnancy.
Significant Differential Effects of Hormone Therapy or Tibolone on Markers of Cardiovascular Disease in Postmenopausal Women
Authors: Koh Kwang Kon , Ahn Jeong Yeal , Jin Dong Kyu , Yoon Byung-Koo , Kim Hyung Sik , Kim Dae Sung , Kang Woong Chol , Han Seung Hwan , Choi In Suck , Shin Eak Kyun
Published: August 2003

Objective—

The objective was to compare the effects of tibolone and hormone therapy (HT) on lipid profile, vasodilation, and factors associated with inflammation and hemostasis.

Methods and Results—

Fifty-three women received micronized progesterone (MP, 100 mg) with conjugated equine estrogen (CEE, 0.625 mg) or tibolone (2.5 mg) daily for 2 months, with a 2-month washout period. Compared with HT, tibolone significantly reduced total cholesterol (
P
<0.001), triglyceride (
P
<0.001), and HDL cholesterol (
P
<0.001) levels as well as triglyceride/HDL cholesterol ratios (
P
<0.001) but not LDL cholesterol levels. Tibolone significantly improved flow-mediated brachial artery dilator response to hyperemia from baseline values (
P
<0.001) by a magnitude similar to that found with HT (
P
=0.628). Compared with tibolone, which showed no changes, HT significantly increased high-sensitivity C-reactive protein (hsCRP,
P
=0.030) and reduced antithrombin III (
P
<0.001). HT and tibolone significantly increased prothrombin fragment 1+2 (F1+2) from baseline values (
P
<0.001 and
P
=0.004, respectively). The effects of HT and tibolone on hsCRP, antithrombin III, and F1+2 were significantly different. HT and tibolone significantly reduced plasma levels of plasminogen activator inhibitor type 1 antigen from baseline levels (
P
=0.006 and
P
=0.005, respectively) to a similar degree (
P
=0.988).

Conclusions—

Tibolone significantly improved flow-mediated brachial artery dilator response by a magnitude similar to that found with CEE+MP; however, tibolone did not significantly change hsCRP and antithrombin III, and tibolone increased F1+2 less than did CEE+MP.
Withdrawal of Cerivastatin Induces Monocyte Chemoattractant Protein 1 and Tissue Factor Expression in Cultured Vascular Smooth Muscle Cells
Authors: Brandes R.P. , Beer S. , Ha T. , Busse R.
Published: August 2003

Objective—

The withdrawal of 3-hydroxy-3-methylglutaryl-coenzyme A-reductase inhibitors (statins) deteriorates endothelial function. We determined in vascular smooth muscle cells whether statin withdrawal leads to the expression of proinflammatory genes involved in the development and progression of arteriosclerosis.

Methods and Results—

The withdrawal of cerivastatin from pretreated vascular smooth muscle cells induced an increase in monocyte chemoattractant protein 1 (MCP-1) and tissue factor (TF) mRNA expression and enhanced MCP-1 secretion as well as cell surface TF activity. In the presence of cerivastatin, this effect was mimicked by geranylgeranyl pyrophosphate or mevalonate. Withdrawal-induced MCP-1 expression was sensitive to PD98059, SB203580, and diphenylene iodonium, suggesting an involvement of extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase, and the NADPH oxidase. Withdrawal increased the activity of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase and enhanced radical generation. Because the latter effect may result from an Rac-mediated activation of the NADPH oxidase, the effect of withdrawal on Rac translocation was studied. Statin treatment induced an increase in Rac-1 content in the cytoplasm. On withdrawal, however, an “overshoot” translocation of Rac to the plasma membrane occurred.

Conclusions—

These observations suggest that statin withdrawal results in the activation of Rac and enhanced oxidative stress. The subsequent activation of redox-activated signal-transduction cascades results in the expression of MCP-1 and TF.
Differential Involvement of the P2Y
1
and P2Y
12
Receptors in Platelet Procoagulant Activity
Authors: Léon Catherine , Ravanat Catherine , Freund Monique , Cazenave Jean-Pierre , Gachet Christian
Published: August 2003

Objective—

In vivo, activated platelets contribute to the initiation of thrombin generation through the exposure of phosphatidylserine to form a procoagulant catalytic surface and through platelet-leukocyte interactions, which lead to the exposure of leukocyte tissue factor (TF). On the basis of observations that the platelet P2Y
1
and P2Y
12
receptors both contribute to thrombosis and thrombin formation in an in vivo model of TF-induced thromboembolism, we further characterized the role of these receptors in thrombin generation.

Methods and Results—

By using the selective P2 antagonists MRS2179 and AR-C69931MX, the P2Y
12
receptor was found to be involved in thrombin-induced exposure of PS on isolated platelets and consequently in TF-induced thrombin formation in platelet-rich plasma. By contrast, the P2Y
1
receptor was not involved in phosphatidylserine exposure nor in thrombin generation in platelet-rich plasma. In addition, both receptors were found to contribute to the interactions between platelets and leukocytes mediated by platelet P-selectin exposure, which result in TF exposure at the surface of leukocytes.

Conclusions—

Overall, these results point to a differential involvement of the 2 platelet ADP receptors in the generation of thrombin and provide further evidence for the relevance of molecules targeting these receptors as antithrombotic agents.
Gender Differences in Postprandial Ketone Bodies in Normolipidemic Subjects and in Untreated Patients With Familial Combined Hyperlipidemia
Authors: Halkes C.J.M. , van Dijk H. , Verseyden C. , de Jaegere P.P.Th. , Plokker H.W.M , Meijssen S. , Erkelens D.W. , Cabezas M. Castro
Published: August 2003

Objective—

An increased hepatic flow of free fatty acids (FFAs) is associated with impaired peripheral FFA trapping by malfunctioning of the complement component 3 (C3)/acylation-stimulating protein system and overproduction of VLDL in familial combined hyperlipidemia (FCHL). Postprandial ketone bodies reflect FFA oxidation in the liver, but the postprandial changes in male and female patients separately have not been determined yet. Gender differences in postprandial ketone bodies and C3 changes were investigated in normolipidemic patients and patients with untreated FCHL.

Methods and Results—

Thirty-two normolipidemic patients (16 female and 16 male) and 19 patients with untreated normolipidemia (9 female and 10 male) underwent an oral fat-loading test. Total and incremental areas under the curves (AUC and dAUC, respectively) after the oral fat load were calculated. Triglyceride AUC was similar between genders in each group. Normolipidemic female subjects showed a higher levels of dAUC-hydroxybutyric acid than male subjects (1.37±0.49 and 0.98±0.43 mmol · h/L). In FCHL, a similar trend was observed in female (1.92±0.38) compared with male (1.55±0.87) subjects. In contrast to normolipidemia, FCHL did not show a postprandial increase in C3, although C3 was higher in FCHL.

Conclusions—

Women have higher postprandial ketone bodies than men, probably reflecting enhanced postprandial hepatic FFA oxidation. In FCHL, both genders have higher postprandial ketone bodies and therefore higher hepatic FFA delivery. The higher fasting and postprandial C3 levels in FCHL may reflect resistance of the C3/acylation-stimulating protein system to promote peripheral fatty acid trapping.
C-Reactive Protein and Coronary Artery Calcification
Authors: Reilly Muredach P. , Wolfe Megan L. , Localio A. Russell , Rader Daniel J.
Published: August 2003

Objective—

Circulating levels of C-reactive protein (CRP) predict cardiovascular events. In contrast, an association between CRP and direct measures of atherosclerosis has not been established clearly. In the largest study to date, we examined the association of plasma CRP with coronary artery calcification (CAC) in 914 asymptomatic subjects in the Study of Inherited Risk of Coronary Atherosclerosis (SIRCA).

Methods and Results—

In age-adjusted, cross-sectional analysis, there was a weak association between plasma CRP levels and CAC in women (odds ratio [OR] for ordinal regression, 1.1 [1.04 to 1.17] per 1.0 mg/L increase in CRP;
P
=0.005) but not in men. The association between CRP and CAC in women remained significant after adjusting for traditional risk factors (OR, 1.08 [1.00 to 1.14];
P
=0.048) but was lost after further adjustment for body mass index (BMI) (OR, 1.02 [0.94 to 1.08];
P
=0.7).

Conclusions—

In SIRCA, CRP was not associated with CAC in men, and a weak association in women was lost after adjustment for BMI. The relation between CRP and clinical events might not be related to atherosclerotic burden. Measures of inflammation, such as CRP, and indices of atherosclerosis, such as CAC, are likely to provide distinct information regarding cardiovascular risk.
Apolipoprotein A-I Deficiency Results in Markedly Increased Atherosclerosis in Mice Lacking the LDL Receptor
Authors: Moore Ryan E. , Kawashiri Masa-aki , Kitajima Ken , Secreto Anthony , Millar John S. , Pratico Domenico , Rader Daniel J.
Published: August 2003

Objective—

An inverse and independent association between plasma levels of apolipoprotein (apo) A-I and coronary heart disease in humans is well established. ApoA-I is the primary protein component of HDL and is thought to play an important role in mediating several of the atheroprotective effects of HDL. However, studies of the effects of apoA-I deficiency on the development of atherosclerosis in mice have not been definitive. We examined the effects of apoA-I deficiency on plasma lipids and atherosclerosis in LDL receptor-deficient mice fed a chow diet for up to 22 months.

Methods and Results—

Both apoA-I-deficient (apoA-I
−/−
)/LDL receptor-deficient (LDLR
−/−
) and LDLR
−/−
mice had a similar moderate elevation of non-HDL cholesterol (non-HDL-C). Unlike previous studies of apoA-I deficiency in which the HDL-C levels were extremely low, the apoA-I
−/−
/LDLR
−/−
mice in this study had substantial levels of HDL-C that were similar to wild-type mice. Despite similar levels of non-HDL-C and substantial levels of HDL-C, apoA-I
−/−
/LDLR
−/−
mice develop significantly more atherosclerosis (up to a 5-fold increase) and oxidant stress (39% increase) than LDLR
−/−
mice.

Conclusions—

These results demonstrate that despite normal levels of HDL-C, apoA-I deficiency is associated with a significant loss of protection from the formation of atherosclerosis in LDLR
−/−
mice fed a chow diet.
Apoptosis Induced by Inhibition of Cyclic AMP Response Element–Binding Protein in Vascular Smooth Muscle Cells
Authors: Tokunou Tomotake , Shibata Rei , Kai Hisashi , Ichiki Toshihiro , Morisaki Takashi , Fukuyama Kae , Ono Hiroki , Iino Naoko , Masuda Satoko , Shimokawa Hiroaki , Egashira Kensuke , Imaizumi Tsutomu , Takeshita Akira
Published: August 2003

Background—

The balance between apoptosis and proliferation of vascular smooth muscle cells (VSMCs) is believed to contribute to the vascular remodeling process. Cyclic AMP response element–binding protein (CREB) is a critical transcription factor for the survival of neuronal cells and T lymphocytes. However, the role of CREB in blood vessels is incompletely characterized.

Methods and Results—

Nuclear staining with Hoechst 33258 or propidium iodine showed an increase in apoptotic cells with activation of caspase-3 in VSMCs infected with adenovirus expressing the dominant-negative form of CREB (AdCREBM1). Basal expression of Bcl-2 and Bcl-2 promoter activity were decreased by infection with AdCREBM1. Immunohistochemistry revealed that CREB was mainly induced and activated in the neointimal α-smooth muscle actin–positive cells of rat carotid artery after balloon injury. Infection with AdCREBM1 suppressed neointimal formation (intima-media ratio) by 33.8% after 14 days of injury, which was accompanied by an increase in apoptosis as indicated by terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling–positive cells and a decrease in bromodeoxyuridine incorporation.

Conclusions—

These results suggest that CRE-dependent gene transcription might play an important role in the survival and proliferation of VSMCs. CREB might be a novel transcription factor mediating the vascular remodeling process and a potential therapeutic target for atherosclerotic disease.
Characterization of Dysfunctional Myocardium by Positron Emission Tomography and Magnetic Resonance
Authors: Knuesel Patrick R. , Nanz Daniel , Wyss Christophe , Buechi Martin , Kaufmann Philip A. , von Schulthess Gustav K. , Lüscher Thomas F. , Schwitter Juerg
Published: August 2003

Background—

Metabolic assessment of dysfunctional myocardium by PET allows prediction of functional recovery after revascularization. Contrast-enhanced MR (ce-MR) discriminates transmural distribution of viable and scar tissue with excellent spatial resolution. Both techniques were applied in ischemic chronic left ventricular dysfunction to relate metabolism and tissue composition to changes of contractile function after revascularization.

Methods and Results—

Nineteen patients with myocardial infarctions (>3 months) were studied by MR and PET, and 10 patients were followed by MR 11±2 months after revascularization. In 56 to 64 segments/heart, systolic wall thickening, viable mass, and thickness of viable rim tissue were determined by MR (inversion-recovery MR with 0.25 mmol/kg Gd-chelate). [
18
F]Fluorodeoxyglucose (FDG) uptake and resting perfusion (
13
N-ammonia) were determined by PET. Viable tissue per segment on ce-MR correlated with FDG uptake per segment (
r
=0.62 and 0.82 for segments with and without flow metabolism mismatch,
P
<0.0001). FDG uptake ≥50% (a predictor of functional recovery) corresponded to a viable rim thickness of 4.5 mm on ce-MR. Thick (>4.5 mm) and metabolically viable segments (≥50% FDG uptake) showed functional recovery in 85%, whereas thin metabolically nonviable segments improved function in 13% (
P
<0.0005). Metabolically viable segments with a thin viable rim and thick segments with reduced FDG uptake improved function in only 36% and 23% of segments, respectively (NS versus thin metabolically nonviable). In these 2 classes of segments, scar per segment was higher than in thick viable segments (
P
<0.0001).

Conclusions—

Metabolism and tissue composition discriminate various classes of dysfunctional myocardium. Most metabolically viable segments with a thick viable rim on ce-MR recover function after revascularization, whereas all other classes showed low recovery rates of contractile function.
Differences in Medical Care and Disease Outcomes Among Black and White Women With Heart Disease
Authors: Jha Ashish K. , Varosy Paul D. , Kanaya Alka M. , Hunninghake Donald B. , Hlatky Mark A. , Waters David D. , Furberg Curt D. , Shlipak Michael G.
Published: August 2003

Background—

The risk of cardiovascular mortality is higher among black women than white women, and the reasons for this disparity are largely unexplored. We sought to evaluate differences in medical care and clinical outcomes among black and white women with established coronary artery disease.

Methods and Results—

Among the 2699 women enrolled in the Heart and Estrogen/progestin Replacement Study (HERS), we used Cox proportional hazards models to determine the association of race with risk of coronary heart disease (CHD) events independent of major cardiovascular risk factors or medical therapies. During an average of 4.1 years of follow-up, CHD events were twice as likely in black compared with white women (6.4 versus 3.1 per 100 person-years, hazard ratio, 2.1; 95% confidence interval, 1.5 to 2.8;
P
<0.001). Black women had higher rates of hypertension, diabetes, and hypercholesterolemia, yet were less likely to receive aspirin or statins. Black women less often had optimal blood pressure (56% versus 63%;
P
=0.01) and LDL cholesterol (30% versus 38%;
P
=0.04) control at baseline and during follow-up. After adjusting for these and other differences, black women still had >50% higher CHD event risk (hazard ratio, 1.52; 95% confidence interval, 1.1 to 2.1;
P
=0.03).

Conclusions—

In a large cohort of women with heart disease, black women less often received appropriate preventive therapy and adequate risk factor control despite a greater CHD event risk. Interventions to improve appropriate therapy and risk factor control in all women, and especially black women, are needed.
Bilateral Versus Unilateral Internal Mammary Revascularization in Patients With Diabetes
Authors: Endo Masahiro , Tomizawa Yasuko , Nishida Hiroshi
Published: August 2003

Background—

This historical cohort study evaluated the benefit of bilateral internal mammary artery (BIMA) grafts in coronary bypass grafting (CABG) for patients with diabetes.

Methods and Results—

We performed elective, isolated, primary, multiple CABG using skeletonized internal mammary artery (IMA) grafts for multivessel disease in 1131 patients, 467 (41.3%) of whom had type 2 diabetes mellitus. The early and long-term results were compared between 277 patients with diabetes using single IMA (SIMA) grafts and 190 using BIMA grafts (median follow-up, 8.1 years). Hospital mortality was similar in both groups. Early patency rate of all grafts was significantly higher using BIMA than using SIMA (97.7% versus 93.8%,
P
=0.0012). Survival rates were not significantly different between SIMA and BIMA groups. Late cardiac mortality was significantly higher in patients with low ejection fraction (0.4 or lower) compared with preserved ejection fraction (higher than 0.4) (
P
=0.0001). In patients with preserved ejection fraction, 10-year survival rate was significantly higher using BIMA than using SIMA (87.8±3.5% versus 75.2±3.4%,
P
=0.04), and 10-year all death–free or repeat CABG or recurrent myocardial infarction–free rate was significantly higher using BIMA than using SIMA (86.6±3.6% versus 69.0±3.7%,
P
=0.0086). The hazard ratio for all death or repeated CABG or recurrent myocardial infarction in patients with preserved ejection fraction was markedly lower in the BIMA group (0.53; 95% CI, 0.31 to 0.9;
P
=0.019).

Conclusions—

Skeletonized BIMA grafts are beneficial in coronary revascularization for diabetic patients with preserved ejection fraction but have limited survival benefit for those with reduced ejection fraction attributable to high cardiac mortality.