bluuebunny/crossref_metadata_2025 huggingface dataset:
GROWTH OF NICKEL NANOSTRUCTURED BEADS AND THIN FILMS
Authors: FOUAD OSAMA A.
Published: April 2008

Ferromagnetic nickel metal beads, fibers, and thin films have been successfully grown from salt solution by a stepwise hydrazine reduction route with and without surfactants. XRD analyses showed that nickel was grown in the metallic phase and no other phases such as nickel oxide were detected in the prepared samples. SEM investigations showed that bead-like structures that agglomerated in the form of cloth- or net-like structures of about 1 μm size that composed of needle-like nanoparticles have been synthesized without using a surfactant. Sharp decrease in size was observed when sodium dodecyl benzene sulphonate (SDBS) and/or polyethylene glycol (PEG) were used. Bead-like morphology of nickel nanostructures of < 150 nm were deposited in this case. Free-standing nickel thin film structures that composed of needle-like nanoparticles of about 50 nm size were deposited by a stepwise reduction. Nickel nanostructures of < 100 nm showed higher coercivity (Hc) value of 184.6,Oe and lower saturation magnetization (Ms) value of 13.29 emu/g. This might be due to the anisotropic shape and size effects. It is strongly believed that nickel nanoparticles are self-assembled through a dipolar–dipolar interaction due to the magnetic property.
ELECTRON TRANSPORT THROUGH MULTILEVEL QUANTUM DOT
Authors: MAITI SANTANU K.
Published: April 2008

Quantum transport properties through some multilevel quantum dots sandwiched between two metallic contacts are investigated by the use of Green's function technique. Here, we do parametric calculations, based on the tight-binding model, to study the transport properties through such bridge systems. The electron transport properties are significantly influenced by (a) the number of quantized energy levels in the dots, (b) the dot-to-electrodes coupling strength, (c) the location of the equilibrium Fermi energy E F , and (d) the surface disorder. In the limit of weak-coupling, the conductance (g) shows sharp resonance peaks associated with the quantized energy levels in the dots, while, they get substantial broadening in the strong-coupling limit. The behavior of the electron transfer through these systems becomes much more clearly visible from our study of the current–voltage (I–V) characteristics. In this context, we also describe the noise power of current fluctuations (S) and determine the Fano factor (F) which provides an important information about the electron correlation among the charge carriers. Finally, we explore a novel transport phenomenon by studying the surface disorder effect in which the current amplitude increases with the increase of the surface disorder strength in the strong disorder regime, while, the amplitude decreases in the limit of weak disorder. Such an anomalous behavior is completely opposite to that of bulk disordered system where the current amplitude always decreases with the disorder strength. It is also observed that the current amplitude strongly depends on the system size which reveals the finite quantum size effect.
PROPERTIES OF ZnO NANOWIRES AND FUNCTIONAL NANOCOMPOSITES
Authors: PYRZ RYSZARD
Published: April 2008

One-dimensional structures like nanotubes and nanowires are potential candidates for nanoscale sensors and actuators. Furthermore, the nanoscale cross-section of these elements introduces controllable size effects while the macroscopic length ensures good mechanical coupling to matrix materials and thus reinforcing effects in nanocomposites. Molecular dynamics simulations are employed to study the electronic and mechanical properties of smallest ZnO nanowires. It has been shown that the electronic band structure of nanowires varies with uniaxial strain and this property can be used for sensing deformation state when nanowires are embedded in a polymer matrix.
Collapse Mechanisms of Langmuir Monolayers
Authors: Lee Ka Yee C.
Published: April 2008

When a two-dimensional (2D) film is compressed to its stability limit, it explores the third dimension via collapse. Understanding this 2D-to-3D transition is of great importance as it provides insight into the origin of defects in thin films. This review draws attention to a reversible folding collapse first discovered in model lung surfactant systems and explores the driving forces for this mechanism. The mode of collapse can be tuned by varying the mechanical properties of the film. I present a continuum elastic theory that captures the onset of the observed folding instability and use digital image analysis to analyze the folding dynamics. This article further explores factors that determine the maximum surface pressure a mixed monolayer can sustain and explains the observed phenomenon using the principle of rigidity percolation. The folding transition observed in lipid monolayers described here has also been observed in other systems, including monolayers of nanoparticles.
Structure, Dynamics, and Assembly of Filamentous Bacteriophages by Nuclear Magnetic Resonance Spectroscopy
Authors: Opella Stanley J. , Zeri Ana Carolina , Park Sang Ho
Published: April 2008

Filamentous bacteriophages serve as model systems for the development and implementation of spectroscopic methods suitable for biological supramolecular assemblies. Not only are their coat proteins small and readily prepared in the laboratory, but they also have two primary roles as membrane proteins and as the principal structural element of the virus particles. As a bacterial system, they are readily labeled with stable isotopes, and this has opened possibilities for the many nuclear magnetic resonance (NMR) studies described in this review. In particular, solid-state NMR of aligned samples has been used to determine the three-dimensional structures of both the membrane-bound forms of coat proteins in phospholipid bilayers and structural forms in virus particles, which has led to an analysis of the assembly mechanism for virus particles as they are extruded through the cell membrane.
Energy Flow in Proteins
Authors: Leitner David M.
Published: April 2008

Energy flows anisotropically through the residues and vibrational states of globular proteins. A variety of experimental and computational studies have identified energy transport channels traversing many residues, in some cases connecting functional regions, potentially important in allostery, and in other cases having no apparent function. This property and the diffusion of energy in proteins are mimicked by transport on a percolation cluster. I review work that addresses connections between globular proteins, percolation clusters, and the similarity of energy flow and thermal transport in these systems. I also review experimental and theoretical studies of the anisotropic flow of energy through the vibrational states of a protein, a property that also can be understood by comparison with simple model disordered systems.
Free Energies of Chemical Reactions in Solution and in Enzymes with Ab Initio Quantum Mechanics/Molecular Mechanics Methods
Authors: Hu Hao , Yang Weitao
Published: April 2008

Combined quantum mechanics/molecular mechanics (QM/MM) methods provide an accurate and efficient energetic description of complex chemical and biological systems, leading to significant advances in the understanding of chemical reactions in solution and in enzymes. Here we review progress in QM/MM methodology and applications, focusing on ab initio QM-based approaches. Ab initio QM/MM methods capitalize on the accuracy and reliability of the associated quantum-mechanical approaches, however, at a much higher computational cost compared with semiempirical quantum-mechanical approaches. Thus reaction-path and activation free-energy calculations based on ab initio QM/MM methods encounter unique challenges in simulation timescales and phase-space sampling. This review features recent developments overcoming these challenges and enabling accurate free-energy determination for reaction processes in solution and in enzymes, along with applications.
Chemistry and Photochemistry of Mineral Dust Aerosol
Authors: Cwiertny David M. , Young Mark A. , Grassian Vicki H.
Published: April 2008

It has become increasingly clear that heterogeneous and multiphase chemistry of tropospheric aerosols can change the chemical balance of the atmosphere. In this review, we focus on recent laboratory studies of the heterogeneous and multiphase chemistry and photochemistry of mineral dust aerosol, a large mass fraction of the tropospheric aerosol. Mineral dust aerosol contains a mixture of oxides, clays, and carbonates. Molecular-based studies of reactions of these dust components provide insights into the chemistry of Earth's atmosphere. We discuss several different types of heterogeneous and multiphase reactions, including (a) ozone decomposition, (b) nitrogen dioxide and nitrate photochemistry, and (c) the dissolution and redox chemistry of Fe-containing dust. We also review some of the important chemical concepts that have recently emerged.
Inside a Collapsing Bubble: Sonoluminescence and the Conditions During Cavitation
Authors: Suslick Kenneth S. , Flannigan David J.
Published: April 2008

Acoustic cavitation, the growth and rapid collapse of bubbles in a liquid irradiated with ultrasound, is a unique source of energy for driving chemical reactions with sound, a process known as sonochemistry. Another consequence of acoustic cavitation is the emission of light [sonoluminescence (SL)]. Spectroscopic analyses of SL from single bubbles as well as a cloud of bubbles have revealed line and band emission, as well as an underlying continuum arising from a plasma. Application of spectrometric methods of pyrometry as well as tools of plasma diagnostics to relative line intensities, profiles, and peak positions have allowed the determination of intracavity temperatures and pressures. These studies have shown that extraordinary conditions (temperatures up to 20,000 K; pressures of several thousand bar; and heating and cooling rates of >1012K s−1) are generated within an otherwise cold liquid.
The novel protein kinase C isoforms -δ and -ε modulate caerulein-induced zymogen activation in pancreatic acinar cells
Authors: Thrower Edwin C. , Osgood Sara , Shugrue Christine A. , Kolodecik Thomas R. , Chaudhuri Anamika M. , Reeve Joseph R. , Pandol Stephen J. , Gorelick Fred S.
Published: April 2008

Isoforms of protein kinase C (PKC) have been shown to modulate some cellular responses such as pathological secretion and generation of inflammatory mediators during acute pancreatitis (AP). We propose that PKC also participates in premature zymogen activation within the pancreatic acinar cell, a key event in the initiation of AP. This hypothesis was examined in in vivo and cellular models of caerulein-induced AP using PKC activators and inhibitors. Phorbol ester, 12- O-tetradecanoylphorbol-13-acetate (TPA, 200 nM), a known activator of PKC, enhanced zymogen activation at both 0.1 nM and 100 nM caerulein, concentrations which mimic physiological and supraphysiological effects of the hormone cholecystokinin, respectively, in preparations of pancreatic acinar cells. Isoform-specific PKC inhibitors for PKC-δ and PKC-ε reduced supraphysiological caerulein-induced zymogen activation. Using a cell-free reconstitution system, we showed that inhibition of PKC-δ and -ε, reduced zymogen activation in both zymogen granule-enriched and microsomal fractions. In dispersed acinar cells, 100 nM caerulein stimulation caused PKC-δ and -ε isoform translocation to microsomal membranes using cell fractionation and immunoblot analysis. PKC translocation was confirmed with in vivo studies and immunofluorescence microscopy in pancreatic tissues from rats treated with or without 100 nM caerulein. PKC-ε redistributed from an apical to a supranuclear region following caerulein administration. The signal for PKC-ε overlapped with granule membrane protein, GRAMP-92, an endosomal/lysosomal marker, in a supranuclear region where zymogen activation takes place. These results indicate that PKC-δ and -ε isoforms translocate to specific acinar cell compartments and modulate zymogen activation.
Cellular cross talk in the small intestinal mucosa: postnatal lymphocytic immigration elicits a specific epithelial transcriptional response
Authors: Schjoldager Katrine T.-B. G. , Maltesen Henrik R. , Balmer Sophie , Lund Leif R. , Claesson Mogens H. , Sjöström Hans , Troelsen Jesper T. , Olsen Jørgen
Published: April 2008

During the early postnatal period lymphocytes migrate into the mouse small intestine. Migrating infiltrative lymphocytes have the potential to affect the epithelial cells via secreted cytokines. Such cross talk can result in the elicitation of an epithelial transcriptional response. Knowledge about such physiological cross talk between the immune system and the epithelium in the postnatal small intestinal mucosa is lacking. We have investigated the transcriptome changes occurring in the postnatal mouse small intestine using DNA microarray technology, immunocytochemistry, and quantitative real-time RT-PCR analysis. The DNA microarray data were analyzed bioinformatically by using a combination of projections to latent structures analysis and functional annotation analysis. The results show that infiltrating lymphocytes appear in the mouse small intestine in the late postweaning period and give rise to distinct changes in the epithelial transcriptome. Of particular interest is the expression of three genes encoding a mucin ( Muc4), a mucinlike protein ( 16000D21Rik), and ATP citrate lyase (Acly). All three genes were shown to be expressed by the epithelium and to be upregulated in response to lymphocytic migration into the small intestinal mucosa.
Cyclic AMP accelerates calcium waves in pancreatic acinar cells
Authors: Shah Ahsan U. , Grant Wayne M. , Latif Sahibzada U. , Mannan Zahir M. , Park Alexander J. , Husain Sohail Z.
Published: April 2008

Cytosolic Ca2+(Ca[Formula: see text]) flux within the pancreatic acinar cell is important both physiologically and pathologically. We examined the role of cAMP in shaping the apical-to-basal Ca2+wave generated by the Ca2+-activating agonist carbachol. We hypothesized that cAMP modulates intra-acinar Ca2+channel opening by affecting either cAMP-dependent protein kinase (PKA) or exchange protein directly activated by cAMP (Epac). Isolated pancreatic acinar cells from rats were stimulated with carbachol (1 μM) with or without vasoactive intestinal polypeptide (VIP) or 8-bromo-cAMP (8-Br-cAMP), and then Ca[Formula: see text] was monitored by confocal laser-scanning microscopy. The apical-to-basal carbachol (1 μM)-stimulated Ca2+wave was 8.63 ± 0.68 μm/s; it increased to 19.66 ± 2.22 μm/s (* P < 0.0005) with VIP (100 nM), and similar increases were observed with 8-Br-cAMP (100 μM). The Ca2+rise time after carbachol stimulation was reduced in both regions but to a greater degree in the basal. Lag time and maximal Ca2+elevation were not significantly affected by cAMP. The effect of cAMP on Ca2+waves also did not appear to depend on extracellular Ca2+. However, the ryanodine receptor (RyR) inhibitor dantrolene (100 μM) reduced the cAMP-enhancement of wave speed. It was also reduced by the PKA inhibitor PKI (1 μM). 8-(4-chloro-phenylthio)-2′- O-Me-cAMP, a specific agonist of Epac, caused a similar increase as 8-Br-cAMP or VIP. These data suggest that cAMP accelerates the speed of the Ca2+wave in pancreatic acinar cells. A likely target of this modulation is the RyR, and these effects are mediated independently by PKA and Epac pathways.
Functional characterization, localization, and molecular identification of rabbit intestinal N-amino acid transporter
Authors: Talukder Jamilur R. , Kekuda Ramesh , Saha Prosenjit , Prasad Puttur D. , Ganapathy Vadivel , Sundaram Uma
Published: April 2008

We have characterized the Na-glutamine cotransporter in the rabbit intestinal crypt cell brush border membrane vesicles (BBMV). Substrate specificity experiments showed that crypt cell glutamine uptake is mediated by system N. Real-time PCR experiments showed that SN2 (SLC38A5) mRNA is more abundant in crypt cells compared with SN1 (SLC38A3), indicating that SN2 is the major glutamine transporter present in the apical membrane of the crypt cells. SN2 cDNA was obtained by screening a rabbit intestinal cDNA library with human SN1 used as probe. Rabbit SN2 cDNA encompassed a 473-amino-acid-long open reading frame. SN2 protein displayed 87% identity and 91% similarity to human SN2. Functional characterization studies of rabbit SN2 were performed by using vaccinia virus-mediated transient expression system. Substrate specificity of the cloned transporter was identical to that of SN2 described in the literature and matched well with substrate specificity experiments performed using crypt cell BBMV. Cloned rabbit SN2, analogous to its human counterpart, is Li+tolerant. Hill coefficient for Li+activation of rabbit SN2-mediated uptake was 1. Taken together, functional data from the crypt cell BBMV and the cloned SN2 cDNA indicate that the crypt cell glutamine transport is most likely mediated by SN2.
Cytokine responses to acute and chronic exercise in multiple sclerosis
Authors: Castellano Vanessa , Patel Darpan I. , White Lesley J.
Published: April 2008

Regular exercise reduces functional loss associated with multiple sclerosis (MS). However, the impact of exercise on inflammatory mediators associated with disease activity remains relatively unexplored. The purpose of this study was to determine whether ambulatory MS subjects would respond similarly to aerobic cycle training compared with matched controls on circulating immune variables, interleukin (IL)-6, tumor necrosis factor (TNF)-α and interferon (IFN)-γ. Eleven MS and 11 non-MS control subjects (8 women and 3 men in both groups) matched in age, height, body mass, body fat, and peak O2uptake completed the study. Subjects completed 30 min of cycle ergometry at 60% of peak O2uptake, 3 day/wk for 8 wk. Plasma cytokine concentrations were determined before and after exercise at weeks 0, 4, and 8. MS and control subjects showed a similar cytokine responses to exercise. IL-6 at rest tended to decrease ( P = 0.08) with training in both groups. Resting plasma TNF-α tended to be higher in MS compared with controls throughout the study ( P = 0.08). MS subjects showed elevated resting TNF-α in MS at the end of the 8-wk program ( P = 0.04), whereas resting TNF-α remained unchanged in controls ( P > 0.05). Resting plasma IFN-γ at rest was elevated in MS subjects ( P = 0.008) and unchanged in controls at the end of the intervention ( P > 0.05). The response of plasma IL-6, TNF-α, and IFN-γ after a single bout of exercise was similar between MS and control subjects ( P > 0.05). Additional research to understand the impact of exercise on immune variables in MS is warranted.
Functional Voltage-Gated Sodium Channels Are Expressed in Human Intestinal Epithelial Cells
Authors: Barshack Iris , Levite Mia , Lang Alon , Fudim Ella , Picard Orit , Ben Horin Shomron , Chowers Yehuda
Published: April 2008

Background and Aim: Local anesthetics which preferentially interact with voltage-gated sodium channels (VGSCs) were shown to have a clinical beneficial effect in ulcerative colitis and to regulate the secretion of inflammatory mediators from intestinal epithelial cells. However, expression of VGSCs in epithelial cells was not demonstrated. Herein we assessed whether intestinal epithelial cells express VGSCs. Methods: The expression of VGSCs in normal human colonic tissue and in the TNFα-treated or untreated intestinal epithelial cell line HT-29 was studied by immunofluorescence staining and FACS analysis, Western blot, immunohistochemistry, and RT-PCR using primers specific for several VGSC α subunits. The function of VGSCs was assessed by measuring changes in the membrane potential of the intestinal epithelial cells following incubation with lidocaine, veratridine, or both. Results: HT-29 cells were shown to express the VGSC α protein. mRNA analysis revealed the expression of nine of ten VGSC α isoforms. Immunohistochemical staining of normal colonic tissue confirmed the expression of VGSCs in colonic epithelial cells, smooth muscle cells, and nerves. Lidocaine induced membrane depolarization of HT-29 cells and its effect was blocked by veratridine. Conclusion: Malignant and normal intestinal epithelial cells express functional VGSCs. These molecules may play a role in the regulation of inflammation in gut physiology and pathology.
Guiding Manometry Probes into the Human Small Bowel without X-Ray: Validation of a New Technique
Authors: v. Schönfeld J.
Published: April 2008

Background: In order to perform small bowel manometry studies in man, the probes have to be guided through the upper gastrointestinal tract. This is usually controlled by fluoroscopy, but a method that allows to place the tubes without X-rays is obviously desirable. Methods: A new method that controls tube placing by sonography and pH-metry instead of X-rays is described. In a total of 19 volunteers 40 tubes were placed, either under fluoroscopic control (n = 22) or without X-rays (n = 18). Results: Nose to antrum time was not significantly different between the two groups (8 ± 2 vs. 10 ± 2 min), but the documented transit of the tube from the antrum into the duodenum was significantly slower in the fluoroscopy group (80 ± 20 vs. 60 ± 12 min). Small bowel transit time was not significantly different between the groups (73 ± 16 vs. 65 ± 15 min). Conclusion: Placing motility probes in the human small bowel can be controlled by sonography and pH-metry instead of fluoroscopy. It is also easily performed, faster and more convenient for the investigator. As far as basic gastrointestinal research is concerned, in Germany less bureaucratic paperwork is involved, as these studies need not be approved by the ‘Bundesamt für Strahlenschutz’ any more.
Podocyte Injury Induced by Albumin Overload in vivo and in vitro: Involvement of TGF-Beta and p38 MAPK
Authors: Yoshida Shigetaka , Nagase Miki , Shibata Shigeru , Fujita Toshiro
Published: April 2008

Background: Proteinuria is a well-established exacerbating factor in chronic kidney disease. Although the mechanisms of albumin-induced tubulointerstitial damage have been extensively studied, the influence of proteinuria on podocytes has not been sufficiently elucidated. The present study examined the effect of albumin overload on podocytes in vivo and in vitro and explored the underlying mechanisms. Methods: Rat podocytes were exposed to albumin overload in vivo by the intraperitoneal injection of albumin over 2 days whilst cultured podocytes were subjected to albumin in vitro. We analyzed albumin uptake, podocyte apoptosis, staining for F-actin and nephrin and involvement of TGF-β1 and p38 MAPK cascades. Results: Rats administered albumin exhibited massive proteinuria and podocyte injury manifested by decreased nephrin immunostaining and foot process effacement. These abnormalities were accompanied by albumin deposition, TGF-β1 upregulation, p38 MAPK phosphorylation and an increased number of glomerular TUNEL-positive cells. Exposure of cultured podocytes to albumin caused actin disarrangement and apoptosis. Podocyte injury was preceded by albumin uptake, induction of TGF-β1 and phosphorylated p38 MAPK. Treatment of podocytes with anti-TGF-β1 neutralizing antibody or SB203580 significantly reduced the albumin-induced injury. Conclusions: These results indicate that albumin overload in vivo and in vitro promotes podocyte injury mainly via TGF-β1/p38 MAPK pathways.
Capsaicin Inhibits Proliferation of Endometriotic Cells in vitro
Authors: Wu Yan , Starzinski-Powitz Anna , Guo Sun-Wei
Published: April 2008

Treatment of immortalized stromal-like and epithelial-like endometriotic cells with capsaicin resulted in inhibition of proliferation in a concentration-dependent manner. In addition, endometriotic cells are more sensitive to capsaicin treatment than immortalized endometrial cells, suggesting that capsaicin may be an admissible drug candidate for treating endometriosis.
Gastric Antral Vascular Ectasia (GAVE): An Update on Clinical Presentation, Pathophysiology and Treatment
Authors: Selinger Christian P. , Ang Yeng S.
Published: April 2008

Gastric antral vascular ectasia (GAVE), though a rare disorder, causes up to 4% of non-variceal upper GI bleeding. This paper gives an overview of studies examining clinical presentation and pathophysiology, and reviews the current evidence for invasive and non-invasive treatments. GAVE is often associated with systemic illnesses, such as cirrhosis of the liver, autoimmune connective tissue disorders, bone marrow transplantation and chronic renal failure. The pathophysiological changes leading to GAVE have not been fully explained and remain controversial. Patient presentation varies from chronic iron-deficiency anaemia to heavy acute gastrointestinal bleeding. It is important to differentiate GAVE from portal hypertensive gastropathy as GAVE does not respond to measures reducing portal pressures. Endoscopic ablation (Nd:YAG-laser or argon plasma coagulation) is the first-line treatment of choice. As evidence for pharmacological therapy with oestrogen (and/or progesterone), tranexamic acid or thalidomide stems from case reports only, these should be used if endoscopic measures have failed to stop chronic blood loss. Surgical antrectomy should be reserved for unresponsive cases as it is associated with a high mortality. Ultimately, treatment of the underlying medical co-morbidities may lead to resolution of GAVE.
Microvascular Injury, Thrombosis, Inflammation, and Apoptosis in the Pathogenesis of Heatstroke
Authors: Roberts George T. , Ghebeh Hazem , Chishti Muhammad A. , Al-Mohanna Falah , El-Sayed Rafaat , Al-Mohanna Futwan , Bouchama Abderrezak
Published: April 2008

Objective—

Severe heatstroke is a leading cause of morbidity and mortality during heat waves. The pathogenesis of tissue injury, organ failure, and death in heatstroke is not well understood.

Methods and Result—

We investigated the pathways of heatstroke-induced tissue injury and cell death in anesthetized baboons (
Papio hamadyras
) subjected to environmental heat stress until core temperature attained 42.5°C (moderate heatstroke; n=3) or onset of severe heatstroke (n=4) signaled by a fall in systolic blood pressure to <90 mm Hg and rise in core temperature to 43.1±0.1°C. Three sham-heated animals served as controls. Light and electron microscopy revealed widespread hemorrhage and thrombosis, transmural migration of leukocytes, and microvascular endothelium injury in severe heatstroke. Immunohistology and ultrastructural analysis demonstrated increased staining of endothelial von Willebrand factor (vWF), tissue factor (TF), and endothelial leukocyte-platelet interaction. Extensive apoptosis was noted in spleen, gut, and lung, and in hematopoeitic cells populating these organs. Double-labeling studies colocalized active caspase-3 and TF with apoptotic cells. Findings in sham-heated animals were unremarkable.

Conclusion—

These data suggested that microvascular injury, thrombosis, inflammation, and apoptosis may play an important role in the pathogenesis of heatstroke injury.
CCN1 Knockdown Suppresses Neointimal Hyperplasia in a Rat Artery Balloon Injury Model
Authors: Matsumae Hironobu , Yoshida Yoshinori , Ono Koh , Togi Kiyonori , Inoue Katsumi , Furukawa Yutaka , Nakashima Yasuhiro , Kojima Yoji , Nobuyoshi Masakiyo , Kita Toru , Tanaka Makoto
Published: April 2008

Objective—

CCN1 (Cyr61) is an extracellular matrix-associated protein involved in cell proliferation and survival. CCN1 is bound to vascular smooth muscle cells (VSMCs) via integrins and is expressed in VSMCs in atherosclerotic lesions, suggesting involvement in the regulation of vascular smooth muscle cell (VSMC) proliferation and atherosclerosis. We hypothesized that knockdown of CCN1 may inhibit VSMC proliferation and suppress neointimal hyperplasia.

Methods and Results—

We examined the effect of the knockdown of CCN1 using rat cultured VSMCs and a rat balloon injury model. CCN1 stimulated adhesion and migration of VSMCs in a dose-dependent manner, and this was blocked by an antibody for integrin α
6
β
1
. Moreover, knockdown of endogenous CCN1 by lentiviral delivery of siRNA significantly inhibited proliferation of VSMCs and the uptake of 5-bromo-2′-deoxyuridine (BrdU). Replenishment with recombinant CCN1 reversed the effect of siRNA knockdown. Interestingly, knockdown of CCN1 significantly suppressed neointimal hyperplasia in a rat carotid artery balloon injury model at days 14 and 28 after injury. Gene transfer of CCN1 to smooth muscle reversed the effect of CCN1 knockdown on neointimal formation. These results suggest that endogenous CCN1 regulates proliferation of VSMCs and neointimal hyperplasia.

Conclusion—

Inhibition of CCN1 may provide a promising strategy for the prevention of restenosis after vascular interventions.
Regulation of Endogenous Apolipoprotein E Secretion by Macrophages
Authors: Kockx Maaike , Jessup Wendy , Kritharides Leonard
Published: April 2008

Apolipoprotein E has critical roles in the protection against atherosclerosis and is understood to follow the classical constitutive secretion pathway. Recent studies have indicated that the secretion of apoE from macrophages is a regulated process of unexpected complexity. Cholesterol acceptors such as apolipoprotein A-I, high density lipoprotein, and phospholipid vesicles can stimulate apoE secretion. The ATP binding cassette transporter ABCA1 is involved in basal apoE secretion and in lipidating apoE-containing particles secreted by macrophages. However, the stimulation of apoE secretion by apoA-I is ABCA1-independent, indicating the existence of both ABCA1-dependent and -independent pathways of apoE secretion. The release of apoE under basal conditions is also regulated, requiring intact protein kinase A activity, intracellular calcium, and an intact microtubular network. Mathematical modeling of apoE turnover indicates that whereas some pools of apoE are committed to either secretion or degradation, other pools can be diverted from degradation toward secretion. Targeted inhibition or stimulation of specific apoE trafficking pathways will provide unique opportunities to regulate the biology of this important molecule.
A Novel RANTES Antagonist Prevents Progression of Established Atherosclerotic Lesions in Mice
Authors: Braunersreuther Vincent , Steffens Sabine , Arnaud Claire , Pelli Graziano , Burger Fabienne , Proudfoot Amanda , Mach François
Published: April 2008

Background—

Atherosclerosis is a chronic inflammatory disease that represents the primary cause of death through coronary disease and stroke. Chemokines are known to play a crucial role in this disease by recruiting inflammatory leukocytes to the endothelium. Recently, the chemokine variant [
44
AANA
47
]-RANTES was shown to impair inflammatory cell recruitment in vivo by interfering with heparin binding and oligomerization.

Methods and Results—

In this study we report that curative treatment with [
44
AANA
47
]-RANTES limits atherosclerotic plaque formation in LDLr
−/−
mice. This was associated with reduced infiltration of T cells and macrophages and reduced production of matrix metalloproteinase (MMP)-9. By contrast, the relative smooth muscle cell and collagen content was increased, indicating a more stable plaque phenotype. In addition, we provide evidence for direct inhibition of leukocyte recruitment into aortic root lesions, attenuated leukocyte rolling and arrest in mesenteric vessels, as well as a reduced proinflammatory response following Con A stimulation in vitro.

Conclusions—

Interference with chemokine oligomerization and chemokine/heparin interactions is a powerful novel approach that inhibits progression of established atherosclerosis in mice. By inhibiting leukocyte recruitment into plaques, [
44
AANA
47
]-RANTES mediates a less inflammatory plaque phenotype and thus reduced systemic inflammatory state.
An Acyltransferase Controls the Generation of Hematopoietic and Endothelial Lineages in Zebrafish
Authors: Xiong Jing-Wei , Yu Qingming , Zhang Jiaojiao , Mably John D.
Published: April 2008

Hematopoietic and endothelial cells develop from a common progenitor, the hemangioblast, or directly from mesodermal cells. The molecular pathway that regulates the specification of both cell lineages remains elusive. Here, we show that a lysocardiolipin acyltransferase,
lycat
, is critical for the establishment of both hematopoietic and endothelial lineages. We isolated
lycat
from the deletion interval of
cloche
, a zebrafish mutant that has dramatically reduced hematopoietic and endothelial cell lineages. Reduction of
lycat
mRNA levels in wild-type zebrafish embryos decreases both endothelial and hematopoietic lineages.
lycat
mRNA rescues blood lineages in zebrafish
cloche
mutant embryos. E165R and G166L mutations in the highly conserved catalytic domain in
Lycat
abolish its function in zebrafish hematopoiesis. Epistasis analysis supports that
lycat
acts upstream of
scl
and
etsrp
in zebrafish hemangioblast development. These data indicate that
lycat
is the earliest known player in the generation of both endothelial and hematopoietic lineages.
Adrenergic Regulation of Cardiac Contractility Does Not Involve Phosphorylation of the Cardiac Ryanodine Receptor at Serine 2808
Authors: MacDonnell Scott M. , García-Rivas Gerardo , Scherman Joseph A. , Kubo Hajime , Chen Xiongwen , Valdivia Héctor , Houser Steven R.
Published: April 2008

The sympathetic nervous system is a critical regulator of cardiac function (heart rate and contractility) in health and disease. Sympathetic nervous system agonists bind to adrenergic receptors that are known to activate protein kinase A, which phosphorylates target proteins and enhances cardiac performance. Recently, it has been proposed that protein kinase A–mediated phosphorylation of the cardiac ryanodine receptor (the Ca
2+
release channel of the sarcoplasmic reticulum at a single residue, Ser2808) is a critical component of sympathetic nervous system regulation of cardiac function. This is a highly controversial hypothesis that has not been confirmed by several independent laboratories. The present study used a genetically modified mouse in which Ser2808 was replaced by alanine (S2808A) to prevent phosphorylation at this site. The effects of isoproterenol (a sympathetic agonist) on ventricular performance were compared in wild-type and S2808A hearts, both in vivo and in isolated hearts. Isoproterenol effects on L-type Ca
2+
current (
I
CaL
), sarcoplasmic reticulum Ca
2+
release, and excitation–contraction coupling gain were also measured. Our results showed that isoproterenol caused significant increases in cardiac function, both in vivo and in isolated hearts, and there were no differences in these contractile effects in wild-type and S2808A hearts. Isoproterenol increased
I
CaL
, the amplitude of the Ca
2+
transient and excitation–contraction coupling gain, but, again, there were no significant differences between wild-type and S2808A myocytes. These results show that protein kinase A phosphorylation of ryanodine receptor Ser2808 does not have a major role in sympathetic nervous system regulation of normal cardiac function.
Ubiquitin-Mediated Stress Response in the Spinal Cord After Transient Ischemia
Authors: Yamauchi Takashi , Sakurai Masahiro , Abe Koji , Matsumiya Goro , Sawa Yoshiki
Published: April 2008

Background and Purpose—

Vulnerability of motor neurons in the spinal cord against ischemia is considered to play an important role in the development of delayed paraplegia after surgery of the thoracic aorta. However, the reasons for such vulnerability are not fully understood. Recently, the ubiquitin system has been reported to participate in neuronal cell death. In the present study, we investigated the expression of ubiquitin system molecules and discussed the relationship between the vulnerability and the ubiquitin system after transient ischemia in the spinal cord.

Methods—

Fifteen minutes of spinal cord ischemia in rabbits was applied with the use of a balloon catheter. In this model, the spinal motor neuron shows selectively delayed neuronal death, whereas other spinal neurons such as interneurons survive. Immunohistochemical analysis and Western blotting for ubiquitin system molecules, ubiquitin, deubiquitylating enzyme (ubiquitin carboxy-terminal hydrolase 1), and ubiquitin-ligase parkin were examined.

Results—

In cytoplasm, ubiquitin and ubiquitin carboxy-terminal hydrolase 1were strongly induced both in interneuron and motor neuron at the early stage of reperfusion, but the sustained expression was observed only in motor neuron. Parkin was induced strongly at 3 hours after the reperfusion, but the immunoreactivity returned to the sham control level at 6 hours in both neurons. In the nuclei, ubiquitin, ubiquitin carboxy-terminal hydrolase 1, and parkin were strongly induced in interneuron, whereas no upregulation of these proteins was observed in motor neuron.

Conclusions—

These results indicate that the vulnerability of motor neuron of the spinal cord might be partially attributed to the different response in ubiquitin-mediated stress response after transient ischemia.
New Brain Lesions After Carotid Stenting Versus Carotid Endarterectomy
Authors: Schnaudigel Sonja , Gröschel Klaus , Pilgram Sara M. , Kastrup Andreas
Published: April 2008

Background and Purpose—

Against the background of a relatively low rate of clinical events during carotid angioplasty and stenting (CAS) or carotid endarterectomy (CEA), diffusion-weighted imaging (DWI) is increasingly being used to compare the incidence of new ischemic lesions after both procedures. In addition, DWI may also provide a means of defining the role of different CAS techniques on this adverse outcome. Therefore, we performed a PubMed search and systematically analyzed all peer-reviewed studies published between January 1990 and June 2007 reporting on the occurrence of new DWI lesions after CAS or CEA.

Summary of Review—

In 32 studies comprising 1363 CAS and 754 CEA procedures, the incidence of any new DWI lesion was significantly higher after CAS (37%) than after CEA (10%) (
P
<0.01). Similar results were obtained in a meta-analysis focusing on those studies directly comparing the incidence of new DWI lesions after either CEA or CAS (OR, 6.1; 95% CI, 4.19 to 8.87;
P
<0.01). The use of cerebral protection devices (33% vs 45% without;
P
<0.01) and closed-cell designed stents during CAS (31% vs 51% with open-cell stents;
P
<0.01), as well as selective versus routine shunt usage during CEA (6% vs 16%;
P
<0.01) significantly reduced the incidence of new ipsilateral DWI lesions.

Conclusions—

New DWI lesions occur more frequently after CAS than after CEA. However, technical advances mainly in the field of endovascular therapy potentially reduce the incidence of these adverse ischemic events. In this scenario, DWI appears to be an ideal tool to compare and further improve both techniques.
MRI Findings in the Painful Poststroke Shoulder
Authors: Shah Rajiv R. , Haghpanah Sepideh , Elovic Elie P. , Flanagan Steven R. , Behnegar Anousheh , Nguyen Vu , Page Stephen J. , Fang Zi-Ping , Chae John
Published: April 2008

Background and Purpose—

We describe the structural abnormalities in the painful shoulder of stroke survivors and their relationships to clinical characteristics.

Method—

Eighty-nine chronic stroke survivors with poststroke shoulder pain underwent T1- and T2-weighted multiplanar, multisequence MRI of the painful paretic shoulder. All scans were reviewed by one radiologist for the following abnormalities: rotator cuff, biceps and deltoid tears, tendinopathies and atrophy, subacromial bursa fluid, labral ligamentous complex abnormalities, and acromioclavicular capsular hypertrophy. Clinical variables included subject demographics, stroke characteristics, and the Brief Pain Inventory Questions 12. The relationship between MRI findings and clinical characteristics was assessed through logistic regression.

Results—

Thirty-five percent of subjects exhibited a tear of at least one rotator cuff, biceps or deltoid muscle. Fifty-three percent of subjects exhibited tendinopathy of at least one rotator cuff, bicep or deltoid muscle. The prevalence of rotator cuff tears increased with age. However, rotator cuff tears and rotator cuff and deltoid tendinopathies were not related to severity of poststroke shoulder pain. In approximately 20% of cases, rotator cuff and deltoid muscles exhibited evidence of atrophy. Atrophy was associated with reduced motor strength and reduced severity of shoulder pain.

Conclusions—

Rotator cuff tears and rotator cuff and deltoid tendinopathies are highly prevalent in poststroke shoulder pain. However, their relationship to shoulder pain is uncertain. Atrophy is less common but is associated with less severe shoulder pain.
Granulocyte-Macrophage Colony-Stimulating Factor Enhances Leptomeningeal Collateral Growth Induced by Common Carotid Artery Occlusion
Authors: Todo Kenichi , Kitagawa Kazuo , Sasaki Tsutomu , Omura-Matsuoka Emi , Terasaki Yasukazu , Oyama Naoki , Yagita Yoshiki , Hori Masatsugu
Published: April 2008

Background and Purpose—

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been reported to accelerate collateral growth (arteriogenesis) at the circle of Willis in rat brain. However, the effect of GM-CSF on leptomeningeal collateral growth has not been established. We examined the effect of unilateral common carotid artery (CCA) occlusion and GM-CSF treatment on leptomeningeal collateral growth in mice.

Methods—

Adult mice were subjected to unilateral CCA occlusion or sham surgery followed by an alternate-day regimen of GM-CSF (20 μg/kg) or saline injection. On day 7, latex perfusion was performed in 1 set of mice to visualize the leptomeningeal vessels, and the number of Mac-2
+
monocytes/macrophages on the dorsal surface of the brain was counted. In another set of mice, on day 7, permanent ipsilateral middle cerebral artery (MCA) occlusion was performed, and infarct volume was measured.

Results—

Leptomeningeal collateral growth was observed after CCA occlusion, and that was enhanced by GM-CSF treatment. An increase in the number of Mac-2
+
cells on the surface of the brain occurred after CCA occlusion and was enhanced by GM-CSF treatment. Seven days after CCA occlusion, GM-CSF treatment decreased the infarct size attributable to subsequent MCA occlusion.

Conclusion—

After CCA occlusion, GM-CSF treatment enhanced leptomeningeal collateral growth and decreased the infarct size after MCA occlusion in mice.
Dual Antithrombotic Therapy Increases Severe Bleeding Events in Patients With Stroke and Cardiovascular Disease
Authors: Toyoda Kazunori , Yasaka Masahiro , Iwade Kazunori , Nagata Ken , Koretsune Yukihiro , Sakamoto Tomohiro , Uchiyama Shinichiro , Gotoh Jun , Nagao Takehiko , Yamamoto Masahiro , Takahashi Jun C. , Minematsu Kazuo
Published: April 2008

Background and Purpose—

We sought to determine the incidence and severity of bleeding events in patients with stroke and cardiovascular diseases who were taking oral antithrombotic agents in Japan, where the incidence of hemorrhagic stroke is higher than in Western countries.

Methods—

A prospective, multicenter, observational study was conducted; 4009 patients who were taking oral antithrombotic agents for stroke and cardiovascular diseases were enrolled. The patients were classified into 4 groups according to their antithrombotic treatment: the single antiplatelet agent group (47.2%); the dual antiplatelet agent group (8.7%); the warfarin group (32.4%); and the warfarin plus antiplatelet agent group (11.7%). The primary end point was life-threatening or major bleeding according to the MATCH trial definition.

Results—

During a median follow-up of 19 months, there were 57 life-threatening and 51 major bleeding events, including 31 intracranial hemorrhages. The annual incidence of the primary end point was 1.21% in the single antiplatelet agent group, 2.00% in the dual antiplatelet agent group, 2.06% in the warfarin group, and 3.56% in the warfarin plus antiplatelet agent group (
P
<0.001). After adjustment for baseline characteristics, adding an antiplatelet agent to warfarin increased the risk of the primary end point (relative risk=1.76; 95% CI, 1.05 to 2.95), and adding another antiplatelet agent to single antiplatelet agent therapy increased the secondary end point of any bleeding, including minor events (relative risk=1.37; 95% CI, 1.07 to 1.76).

Conclusions—

The incidence of bleeding events during antithrombotic therapy in Japan was similar to that reported for Western countries, although the trials used different study designs. Dual antithrombotic therapy was independently related to an increased risk of bleeding events.
Recanalization of an Acute Middle Cerebral Artery Occlusion Using a Self-Expanding, Reconstrainable, Intracranial Microstent as a Temporary Endovascular Bypass
Authors: Kelly Michael E. , Furlan Anthony J. , Fiorella David
Published: April 2008

Background and Purpose—

Although self-expanding intracranial microstents have been used to treat acute middle cerebral artery (MCA) stroke, there are disadvantages associated with placing a permanent endovascular implant. We describe a technique in which a reconstrainable stent was used to provide a temporary endovascular bypass to achieve MCA recanalization without permanent stent implantation.

Methods—

A 55-year-old male presented with acute onset left hemiplegia (National Institutes of Health Stroke Score (NIHSS) of 20. Angiography showed an occluded right cervical internal carotid artery (ICA), a patent anterior communicating artery (ACOMM), and embolic occlusion of the right middle cerebral artery (MCA), M1 segment.

Results—

Working through a 6F guide-catheter positioned in the left cervical ICA, an SL-10 microcatheter, and 0.014-inch Synchro-2 microwire were manipulated across the anterior communicating artery and into the right M1 segment occlusion. 5 mg of abciximab and 3 mg tPA were infused directly into the thrombus through the microcatheter. Mechanical thrombolysis using the microwire and microcatheter was ineffective in achieving any recanalization. An Enterprise stent (4×22 mm) was delivered across the occlusion site and partially unconstrained. The unconstrained portion of the stent expanded and acted as a temporary bypass, to circumferentially displace and structurally disrupt the M1 thrombus, producing immediate revascularization of the right territory MCA. After approximately 20 minutes, the Enterprise stent was reconstrained and removed. Final angiography demonstrated excellent filling of the right M1 and distal MCA branches. The patient improved to an NIHSS of 7, regaining movement of his left upper and lower extremities.

Conclusions—

The temporary endovascular bypass technique yielded immediate and durable revascularization of an acutely occluded middle cerebral artery without the disadvantages associated with the placement of a permanent endovascular stent.