bluuebunny/crossref_metadata_2025 huggingface dataset:
Subcellular Ca2+ Dynamics Measured with Targeted Aequorin in Chromaffin Cells
Authors: ALONSO MARIA TERESA , MONTERO MAYTE , CARNICERO ESTELA , GARCÍA‐SANCHO JAVIER , ALVAREZ JAVIER
Published: July 2009

Abstract: In the last years, intracellular organella have emerged as key components in the generation and transduction of Ca2+ signals in adrenal chromaffin cells. Therefore, accurate measurements of Ca2+ inside cytoplasmic organella are essential for a comprehensive analysis of the Ca2+ redistribution that follows cell stimulation. We have engineered the Ca2+‐sensitive photoprotein aequorin to monitor selectively Ca2+ within the endoplasmic reticulum and the mitochondria. The targeted aequorins were delivered to the appropriate organelles of bovine chromaffin cells by using a herpes simplex virus‐based amplicon vector, which permits efficient gene transfer and high levels of expression in infected cells. We have investigated the relationship between the caffeine and InsP3‐sensitive Ca2+ pools and the presence of the Ca2+‐induced Ca2+ release (CICR) mechanism in chromaffin cells. We find that ER Ca2+ pools responding to caffeine and to InsP3 mostly overlap and that CICR can be induced by Ca2+ entry elicited by high K+ depolarization. Moreover, the activation of Ca2+ channels, either the voltage‐gated Ca2+ channels on the plasma membrane or the channels on the endoplasmic reticulum (ER), generates subplasmalemmal high [Ca2+]c domains that induce Ca2+ uptake by mitochondria. Interestingly, only a subpopulation of mitochondria, the one contained in the pool located close to the plasma membrane and the ryanodine receptors, take up Ca2+ efficiently, and the [Ca2+]M reaches values of 300‐500 μM.
Start‐up Behavior of Viscoelastic Fluid Flow Near a Capillary Entry
Authors: SHIRAKASHI MASATAKA , TAKAHASHI TSUTOMU , WATANABE ATSUSHI , ARUGA YOHSUKE
Published: July 2009

Abstract: The effect of elasticity on the capillary entry flow development process was investigated by applying a laser doppler velocimeter (LDV) and flow visualization. The fluid filling the test section was kept at rest under a pressure of compressed air or a natural head and then a valve below the capillary was quickly opened to start the flow. Although the development of the capillary entry flow field of a Newtonian fluid is virtually quasi‐steady, it takes a considerable time for a viscoelastic PAA‐solution to attain its terminal regime. The transient behavior of the flow rate of the PAA‐solution is attributed to the gradual development process of the flow field upstream from the entry.
Measurement of the Density of CO2 Solution by Mach‐Zehnder Interferometry
Authors: SONG YONGCHEN , NISHIO MASAHIRO , CHEN BAIXIN , SOMEYA SATOSHI , UCHIDA TSUTOMU , AKAI MAKOTO
Published: July 2009

Abstract: The density of CO2 solution was measured by using Mach‐Zehnder interferometry in the pressure range from 5.0 to 12.5 MPa, at temperatures from 273.25 to 284.15 K, and CO2 mass fraction in solution up to 0.061. It was found that the density difference between the CO2 solution and pure water at the same pressure and temperature is monotonically linear with the CO2 mass fraction. The slope of this linear function, calculated by experimental data fitting, is 0.275.
Multiphase Bubbly Flow Visualization Using Particle Image Velocimetry
Authors: HASSAN YASSIN A.
Published: July 2009

Abstract: This article describes advances made in using particle image velocimetry (PIV) techniques in the study of multiphase bubbly flow. One of the fundamental issues in bubbly flow is the prediction of the velocity field. A methodology that allows for velocity field measurements of both components of a two‐phase bubbly flow is presented. The bubble shape is also constructed via a shadow imaging technique combined with PIV.
Visualization of Bubble‐Fluid Interaction by a Moving Object Flow Image Analyzer System
Authors: CHOI H. M. , TERAUCHI T. , MONJI H. , MATSUI G.
Published: July 2009

Abstract: This paper deals with interaction between a bubble and fluid around it, visualized by a moving object flow image analyzer (MOFIA) consisting of a three‐dimensional (3D) moving object image analyzer (MOIA) and two‐dimensional particle image velocimetry (PIV). The experiments were carried out for rising bubbles of various sizes and shapes in stagnant water in a vertical pipe. In the MOFIA employed, 3D‐MOIA was used to measure bubble motion and PIV to measure fluid flow. The 3D position and shape of a bubble and the velocity field were measured simultaneously. The experimental results showed that the interaction was characterized by the shape, size and density of a bubble. Concretely, they showed the characteristics of bubble motion, wake shedding, and flow field.
Effect of Electrolytes on Bubble Coalescence in Columns Observed with Visualization Techniques
Authors: AGUILERA MARÍIA EUGENIA , OJEDA ANTONIETA , RONDÓN CAROLINA , LÓPEZ DE RAMOS AURA
Published: July 2009

Abstract: Bubble coalescence and the effect of electrolytes on this phenomenon have been previously studied. This interfacial phenomenon has attracted attention for reactor design/operation and enhanced oil recovery. Predicting bubble coalescence may help prevent low yields in reactors and predict crude oil recovery. Because of the importance of bubble coalescence, the objectives of this work were to improve the accuracy of measuring the percentage of coalescing bubbles and to observe the interfacial gas‐liquid behavior. An experimental setup was designed and constructed. Bubble interactions were monitored with a visualization setup. The percentage of air bubble coalescence was 100% in distilled water, about 50% in 0.1 M sodium chloride (NaCl) aqueous solution, and 0% in 0.145 M NaCl aqueous solution. A reduction of the contact gas‐liquid area was observed in distillate water. The volume of the resulting bubble was the sum of the original bubble volumes. Repulsion of bubbles was observed in NaCl solutions exceeding 0.07 M. The percentage of bubble coalescence diminishes as the concentration of NaCl chloride increases. High‐speed video recording is an accurate technique to measure the percentage of bubble coalescence, and represents an important advance in gas‐liquid interfacial studies.
X‐ray‐Based Flow Visualization and Measurement
Authors: SEEGER AXEL , AFFELD KLAUS , GOUBERGRITS LEONID , KERTZSCHER ULRICH , WELLNHOFER ERNST , DELFOS RENE
Published: July 2009

Abstract: Information concerning continuous or discreet phase flow in multiphase systems is desired for various practical and analytical applications. The potential of X‐ray‐based flow visualization and measurement of multiphase flow is demonstrated here by two non‐intrusive methods: (1) Measurement of the three‐dimensional (3D) velocity field of the continuous liquid phase in a bubble column by X‐ray‐based particle tracking velocimetry (PTV) of seeded particles. (2) Liquid flow visualization in a bubble column by injecting an X‐ray absorbing liquid into the bubble column. X‐rays have the advantage that they are not affected by the various refraction indices of the multiphase system and penetrate the multiphase flow in undistorted straight lines. Hence, in contrast to optical methods, both of these X‐ray‐based methods are independent of the void fraction and are applicable to opaque liquids.
Visualization of Jet Flows over a Plate by Pressure‐Sensitive Paint Experiments and Comparison with CFD
Authors: FUJII KOZO , TSUBOI NOBUYUKI , FUJIMATSU NOBUYOSHI
Published: July 2009

Abstract: Flow fields created by underexpanded sonic jets impinging on an inclined flat plate were studied experimentally using the pressure sensitive paint (PSP) measurement technique. The measurement system and some representative results are presented here. Two binders, thin‐layer chromatography (TLC) plates and anodized aluminum (A‐A) plates were tested with bathophen ruthenium chloride as a luminophore. The results show that both the binders can be used. TLC plates are preferable because their luminescent intensity is almost twice that of the A‐A plates. Quantitative measurements require accurate temperature calibration. A preliminary effort to elucidate the flow structure by combining the PSP results with a computer simulation of the same flow field is presented. Although good agreement is obtained between the experimental and numerical results, future quantitative comparisons are necessary to yield a useful tool in the analysis of the jet‐plate interaction flows.
Visualization and Phase Doppler Particle Analysis Measurements of Oscillating Spray Propagation of an Airblast Atomizer under Typical Engine Conditions
Authors: SCHOBER PETER , MEIER ROBERT , SCHÄFER OLAF , WITTIG SIGMAR
Published: July 2009

Abstract: Propagation of a kerosene spray formed by a prefilming airblast atomizer within a pulsating flame has been investigated. The measurements were performed in a 400 kW single combustor rig at typical engine conditions of up to 0.8 MPa inlet pressure and 673 K inlet temperature. The homogeneity of the fuel spray propagation in the reacting zone substantially influences the local temperature distribution in the reaction zone and, therefore, the formation of thermal NOχ. Phase locked visualization of the spray propagation and the flame luminescence was applied to the pulsating combustion process in order to analyze the complex interaction between the time dependent flow field, the spray propagation, and the combustion process. The spray characteristic was additionally investigated by means of time resolved PDPA measurements in the reacting flow.
Measurement of a Velocity Field in Microvessels Using a High Resolution PIV Technique
Authors: SUGII YASUHIKO , NISHIO SHIGERU , OKAMOTO KOJI
Published: July 2009

Abstract: Because endothelial cells are subject to flow shear stress, it is important to determine the velocity distribution in microvessels during studies of the mechanical interactions between the blood and the endothelium. Particle image velocimetry (PIV) is a quantitative method for measuring velocity fields instantaneously in experimental fluid mechanics. The authors have developed a high‐resolution PIV technique that improves the dynamic flow range, spatial resolution, and measurement accuracy. The proposed method was applied to images of the arteriole in the rat mesentery, using an intravital microscope and high‐speed digital video system. Taking the mesentery motion into account, the PIV technique was improved to measure red blood cell (RBC) velocity. Velocity distributions with spatial resolutions of 0.8 3 0.8 mm were obtained even near the wall in the center plane of the arteriole. The arteriole velocity profile was blunt in the center region of the vessel cross‐section and sharp in the near‐wall region. Typical flow features for non‐Newtonian fluid are shown.
The Effects of Peroxisome Proliferators on Global Lipid Homeostasis and the Possible Significance of These Effects to Other Responses to These Xenobiotics
Authors: XIE YI , YANG QIAN , DePIERRE JOSEPH W.
Published: July 2009

Abstract: Peroxisome proliferators (PPs) have been shown to regulate hepatic lipid metabolism via activation of the peroxisome proliferator‐activated receptor alpha (PPAR‐α). Recent studies have revealed that PPs also exert considerable influence on certain extrahepatic tissues, including adipose tissue and lymphoid organs, in an indirect fashion. Inhibition of the proliferation of thymocytes and splenocytes and alteration of fatty acid uptake into and release from adipose tissue might be consequences of the hypolipidemic effect of PPs involving both PPARα‐dependent and ‐independent pathways. Exposure to PPs reduces the cholesterol content of circulating low‐density lipoprotein (LDL), which is the major supply of this steroid to most peripheral tissues. In addition, PPs increase serum levels of high‐density lipoprotein (HDL), which extracts cholesterol from peripheral tissues and returns it to the liver, thereby further decreasing the cholesterol content of peripheral tissues. This net flux of cholesterol from extrahepatic tissues to the liver represents a change in global lipid homeostasis. In normal healthy young mice, this hypolipidemic effect could result in loss of cholesterol and other lipids from peripheral tissues (e.g., adipose tissue, thymus, and spleen), especially from plasma membrane caveolae, which might perturb normal cellular signaling and result in tissue atrophy. On the other hand, the increased hepatic cholesterol content in the hepatocyte plasma membrane might actually enhance signaling, playing a role in the liver hypertrophy and hepatocarcinogenecally associated with long‐term PP treatment. In conclusion, it is important to consider the systemic effects of PPs, rather than to focus on the liver alone.
Space Flight and Insulin‐like Growth Factor‐I Signaling in Rat Osteoblasts
Authors: KUMEI YASUHIRO , NAKAMURA HIROSHI , MORITA SADAO , AKIYAMA HIDEO , HIRANO MASAHIKO , OHYA KEI'ICHI , SHINOMIYA KEN'ICHI , SHIMOKAWA HITOYATA
Published: July 2009

Abstract:The primary culture of rat osteoblasts was treated with 1α,25 dihydroxyvitamin D3and fixed with guanidine isothiocyanate solution during a space shuttle flight. The mRNA levels were analyzed by quantitative reverse transcription‐polymerase chain reaction. Microgravity decreased the mRNA levels of insulin‐like growth factor‐I (IGF‐I) and increased reciprocally the IGF‐I receptor mRNA levels, as compared to the ground (1 ×g) control. Microgravity completely suppressed the mRNA expression of the insulin receptor substrate‐1, the postreceptor signaling molecule of IGF‐I. Microgravity might deteriorate the action and signaling of IGF‐I in rat osteoblasts.
α‐Thrombin Activates Akt via a Nonreceptor Tyrosine Kinase in IIC9 Cells
Authors: PHILLIPS‐MASON POLLY J. , GOEL REEMA , BALDASSARE JOSEPH J.
Published: July 2009

Abstract: Previous data from our laboratory show that PI 3‐kinase is required for α‐thrombin‐stimulated G1 progression in IIC9 cells. In IIC9 cells, PI 3‐kinase acts downstream of Ras to activate Akt, in a pathway parallel to ERK1. Here we show that α‐thrombin does not transactivate either the EGF receptor or the PDGF receptor as measured by tyrosine phosphorylation, suggesting that activation of PI 3‐kinase by α‐thrombin is not the result of an RTK. Interestingly, both genistein and PP1 block α‐thrombin‐stimulated Akt phosphorylation, suggesting the involvement of a member of the Src family of nonreceptor tyrosine kinases.
Activation of ERK, Controlled by Rac1 and Cdc42 via Akt, Is Required for Anoikis
Authors: RUL WILFRID , ZUGASTI OLIVIER , ROUX PIERRE , PEYSSONNAUX CAROLE , EYCHENE ALAIN , FRANKE THOMAS F. , LENORMAND PHILIPPE , FORT PHILIPPE , HIBNER URSZULA
Published: July 2009

Abstract: We have recently reported that two Rho family GTPases, Rac1 and Cdc42, are intimately involved in the control of cell survival of murine fibroblasts linked to adherence to the extracellular matrix. Inhibition of either Rac1 or Cdc42 signaling in adherent cells mimics the loss of anchorage and efficiently induces apoptosis in both immortalized and primary cells. In both cases cell death is dependent on the wild‐type p53 tumor suppressor and is accompanied by activation of endogenous p53. Here, we describe that the inhibition of Rac1 or Cdc42 signaling leads to MAPK ERK activation via a pathway involving PI(3)K, Akt, Raf, and MEK, but not Ras. The moderate level of ERK activation that accompanies anoikis is an essential component of proapoptotic signaling; whereas sustained, high‐intensity ERK signaling promotes survival in the same experimental system.
Curcumin Induces Caspase‐3‐Independent Apoptosis in Human Multidrug‐Resistant Cells
Authors: PIWOCKA KATARZYNA , BIELAK‐MIJEWSKA ANNA , SIKORA EWA
Published: July 2009

Abstract: Curcumin, the major component of the spice turmeric, used in 50‐μM concentration, induced cell death in multidrug‐resistant CEMP‐gp4 and LoVoP‐gp4 cells as well as in their sensitive counterparts as assessed by TUNEL method and morphological observation. In all cells induced to undergo cell death with curcumin, there was no caspase‐3 activation because only the unprocessed form of caspase‐3 was observed using immunoblotting.
Detection and Characterization of Membrane‐Bound Selenoproteins in the Kidney of the Rat
Authors: KYRIAKOPOULOS A. , BERTELSMANN H. , GRAEBERT A. , HOPPE B. , KÜHBACHER M. , BEHNE D.
Published: July 2009

Abstract: The essential trace element selenium is of fundamental importance to human biology. Information on the membrane‐bound selenoproteins was obtained by labeling of rats in vivo with 75Se‐selenite, subcellular fractionation of the tissue homogenates, separation of the proteins by SDS‐PAGE, two‐dimensional electrophoresis, and selenium detection by autoradiography. In this way, in addition to already known membrane‐bound selenoproteins three novel selenoproteins in the molecular mass range of 38–40, 18, and 12–13 kDa were detected in the microsomal membranes.
Regulation of p53
Authors: OREN MOSHE , DAMALAS ALEXANDER , GOTTLIEB TANYA , MICHAEL DAN , TAPLICK JAN , LEAL JUAN FERNANDO MARTINEZ , MAYA RUTH , MOAS MIRI , SEGER RONY , TAYA YOICHI , BEN‐ZE'EV AVRI
Published: July 2009

Abstract: The p53 tumor suppressor protein provides a major anti‐cancer defense mechanism, as underscored by the fact that the p53 gene is the most frequent target for genetic alterations in human cancer. Recent work has led to the realization that p53 lies at the hub of a very complex network of signaling pathways that integrate a variety of intracellular and extracellular inputs. Part of this network consists of an array of autoregulatory feedback loops, where p53 exhibits very intricate interactions with other proteins known to play important roles in the determination of cell fate. We discuss two such loops, one involving the β‐catenin protein and the other centering on the Akt/PKB protein kinase. In both cases, the central module is the interplay between p53 and the Mdm2 protein, which inactivates p53 and targets it for rapid proteolysis. Whereas deregulated β‐catenin can lead to Mdm2 inactivation and p53 accumulation, active p53 can promote the degradation and down‐regulation of β‐catenin. Similarly, Akt can block p53 activation by potentiating Mdm2, whereas activated p53 can tune down Akt in several different ways. In each case, the actual output of the loop is determined by the delicate balance between the opposing effects of its different components. Often, this balance is dictated by additional signaling processes that occur simultaneously within the same cell. Genetic alterations characteristic of cancer are capable of severely distorting this balance, thereby overriding the tumor suppressor effects of p53 in a manner that facilitates neoplastic conversion.
CoCl2, a Chemical Inducer of Hypoxia‐Inducible Factor‐1, and Hypoxia Reduce Apoptotic Cell Death in Hepatoma Cell Line HepG2
Authors: PIRET JEAN‐PASCAL , MOTTET DENIS , RAES MARTINE , MICHIELS CARINE
Published: July 2009

Abstract: HIF‐1 (hypoxia‐inducible factor‐1) is the major transcription factor that is specifically activated during hypoxia. This transcription factor is composed of two subunits: HIF‐1α and ARNT (aryl hydrocarbon receptor nuclear translocator). ARNT is constitutively expressed, whereas HIF‐1α is targeted to proteasome degradation by ubiquitination during normoxia. In hypoxia, HIF‐1α is stabilized and translocates to the nucleus, where it binds to ARNT. The active HIF‐1 induces expression of various genes whose products play an adaptive role to the new conditions induced by hypoxia. Besides the role played by HIF‐1 in the adaptation to hypoxia, recent data describe a possible role for HIF‐1 in the modulation of apoptosis. According to some authors, hypoxia induces apoptosis. However, it has also been reported that hypoxia could protect cells against apoptotic cell death induced by various agents such as serum deprivation and incubation in the presence of chemotherapy agents. These contradictory data suggest that HIF‐1 could display either a proapoptotic or an antiapoptotic role according to the conditions. In order to study how HIF‐1 can modulate apoptosis, we studied whether hypoxia or cobalt chloride, a chemical inducer of HIF‐1, could influence apoptosis induced by tert‐butyl hydroperoxide (t‐BHP), serum deprivation, or both in hepatoma cell line HepG2. HepG2 cells were incubated 8 hours under normoxia or hypoxia in the presence of t‐BHP with or without CoCl2. CoCl2 reduced the apoptotic death of HepG2 cells induced by t‐BHP and serum deprivation, as measured by DNA fragmentation. This effect was confirmed by measurement of the caspase activity. Moreover, hypoxia also prevented t‐BHP‐ or serum deprivation‐induced DNA fragmentation and caspase activation‐however, to a lower extent than CoCl2. These different data suggest a possible antiapoptotic role of HIF‐1. More experiments are needed to define if HIF‐1 actually plays an active role in cell death protection and to determine the exact mechanism underlying this effect.
ERK and Calcium in Activation of HIF‐1
Authors: MOTTET DENIS , MICHEL GAETAN , RENARD PATRICIA , NINANE NOELLE , RAES MARTINE , MICHIELS CARINE
Published: July 2009

Abstract: HIF‐1 (hypoxia‐inducible factor‐1) is the main transcription factor responsible for increased gene expression in hypoxia. The oxygen‐dependent regulation of HIF‐1 activity occurs at multiple levels in vivo. The mechanisms regulating HIF‐1α protein expression have been most extensively analyzed, but the ones modulating HIF‐1 transcriptional activity remain unclear. Changes in the phosphorylation and/or redox status of HIF‐1α certainly play a role. Here, we show that ionomycin could activate HIF‐1 transcriptional activity in a way that is additive to the effect of hypoxia without affecting HIF‐1α protein level and HIF‐1 DNA binding capacity. In addition, a calmodulin dominant‐negative mutant as well as BAPTA, an intracellular calcium chelator, inhibited the hypoxia‐induced HIF‐1 activation. These results indicate that elevated calcium in hypoxia could participate in HIF‐1 activation. PD98059, an inhibitor of the ERK pathway, but not KN‐93, an inhibitor of calmodulin kinases II and IV, also blocked HIF‐1 activation by hypoxia and by ionomycin. Altogether, these results suggest that calcium and calmodulin would act upstream of ERK in the hypoxia signal transduction pathway leading to enhanced HIF‐1 transcriptional activity.
Transcriptional Regulation of the HumanMDR1 Gene at the Level of the Inverted MED‐1 Promoter Region
Authors: LABIALLE STEPHANE , GAYET LANDRY , MARTHINET ERIC , RIGAL DOMINIQUE , BAGGETTO LORIS G.
Published: July 2009

Abstract:The typical multidrug resistance phenotype (MDR), the major cause of failure of cancer chemotherapy, is the result of the overexpression of the humanMDR1 gene, the regulation of which is still incompletely understood. Using several EMSA experiments, we have identified a new regulatory sequence located from −103 to −98 bp relative to the +1 start site in theMDR1 promoter region. This sequence, which we called inverted MED‐1, acts as acis‐activator for this gene. In transient transfection experiments of highly resistant human lymphoblastic CEM/VLB5 cells, its deletion from the promoter region is responsible for 60% inhibition of theMDR1 transcriptional activity. This sequence specifically binds a nuclear protein of about 150–160 kDa. We showed that its binding capacity is related to the chemoresistance level of the studied cell lines and may reflect the increased transcriptional activity of theMDR1 gene in multidrug‐resistant cells.
Diminished Transcription Factor Survival Signals in Dorsal Root Ganglia in Rats with Streptozotocin‐Induced Diabetes
Authors: PURVES TERTIA D. , TOMLINSON DAVID R.
Published: July 2009

Abstract: Rats with experimental diabetes show changes in prenuclear signals that might impact on neuronal transcription factors; these in turn may be responsible for the phenotype switches characteristic of diabetic neuropathies. This study was designed to examine the effect of streptozotocin‐diabetes of 12 weeks' duration on the activation of three transcription factors known to affect neuronal phenotype in dorsal root ganglia (DRG). Pooled L4 and L5 were subject to gel‐shift analysis to measure binding to consensus oligonucleotides. This revealed significant reduction in activation of CREB and NFκB in DRG from diabetic rats, but no effect on AP‐1. The CREB change may be secondary to target tissue NGF depletion, and the reduced NFκB indicates impaired capacity to withstand neurotrophic defects. Thus, these changes my underlie consequences of impaired neurotrophic regulation of phenotype reported in other studies in diabetic rats.
Redox Signaling through NADPH Oxidases: Involvement in Vascular Proliferation and Coagulation
Authors: GÖRLACH AGNES , KIETZMANN THOMAS , HESS JOHN
Published: July 2009

Abstract: Reactive oxygen species (ROS) have been shown to play important functions as signaling molecules in the vasculature. Several NADPH oxidase isoforms have been identified in endothelial and smooth muscle cells, which are largely responsible for basal and stimulated ROS production in these cells. Moreover, evidence increases that activation of these enzymes contributes to stimulation of signaling cascades modulating essential functions in the vasculature such as endothelial and smooth muscle cell proliferation as well as thrombosis.
Redox Control by Dithiol‐Disulfide Exchange in Plants
Authors: JACQUOT JEAN‐PIERRE , ROUHIER NICOLAS , GELHAYE ERIC
Published: July 2009

Abstract: In plants, the photons of light are absorbed at the level of the photosystems in the chloroplasts. The functioning of the photosynthetic electron transfer chain linked to this process is required to generate NADPH and ATP. In addition, the light signal promotes a regulatory cascade, situated in the stroma, that involves ferredoxin, ferredoxin‐thioredoxin reductase, and thioredoxins. This redox‐based signal transduction chain allows fine regulation of stromal enzymes and tight control of the photosynthetic process. The molecular properties and the functioning of this redox regulatory chain will be described in this review.
Effects of Homocysteine on the Cellular Responses of Murine Endothelial Cells Cultured in Vitro
Authors: TACHENY A. , SANTOS S. DOS , HUET A.‐C. , STEENBRUGGE M. VAN , MICHIELS C. , HOLVOET P. , RAES M.
Published: July 2009

Abstract: Homocysteine, derived from the metabolism of methionine, is claimed as a proatherogenic factor that leads to vascular dysfunction. To gain better insight into the molecular mechanisms involved, homocysteine was tested on a model of murine endothelial cells cultured in vitro, using a prototype DNA chip. The DNA chip was designed to follow the expression at the mRNA level of some major proinflammatory genes; TNF‐α was used as a positive control.
Risk Factors for Cerebral Amyloid Angiopathy in the Elderly
Authors: YAMADA MASAHITO
Published: July 2009

Abstract: To elucidate risk factors for cerebral amyloid angiopathy (CAA) in the elderly, we have investigated 201 autopsy cases of elderly Japanese (ages: 62–104 years), including 82 patients with Alzheimer's disease (AD). Severity of CAA showed no relationship with the history of hypertension, hyperlipidemia, or diabetes mellitus, nor with severity of atherosclerosis of cerebral and systemic arteries, indicating that common vascular risk factors would not be related to CAA. Incidence and severity of CAA were significantly higher in the AD cases compared with the non‐AD cases (p < 0.0001). Severity of CAA correlated with densities of senile plaques and neurofibrillary tangles in total and non‐AD cases, although the correlations were not significant within the AD cases. Associations of genetic polymorphisms with CAA have been investigated for genes of apolipoprotein E (APOE), presenilin 1 (PS1), α1‐antichymotrypsin (ACT), butyrylcholinesterase, α2‐macroglobulin, and paraoxonase. Severity of CAA in APOEε4 carriers is significantly higher than that in non‐ε4 carriers in total cases, although no significant difference was found in the CAA severity between the ε4 carriers and non‐ε4 carriers within the AD or non‐AD group. An intronic polymorphism of PS1 was significantly associated with the severity of CAA, indicating that the PS1 2/2 genotype may be related to lower risk of CAA. A polymorphism in the signal peptide sequence of ACT was significantly associated with the CAA severity in the AD group. Our results suggest that CAA shares risk factors with AD and that multiple genetic factors would be associated with the risk of CAA in the elderly.
Atherosclerotic Lesions and Mitochondria DNA Deletions in Brain Microvessels as a Central Target for the Development of Human AD and AD‐Like Pathology in Aged Transgenic Mice
Authors: ALIEV GJUMRAKCH , SEYIDOVA DILARA , NEAL MAXWELL L. , SHI JIONG , LAMB BRUCE T. , SIEDLAK SANDRA L. , VINTERS HARRY V. , HEAD ELIZABETH , PERRY GEORGE , LAMANNA JOSEPH C. , FRIEDLAND ROBERT P. , COTMAN CARL W.
Published: July 2009

Abstract: We have studied the ultrastructural features of vascular lesions and mitochondria in brain vascular wall cells from human AD brain biopsy, human short postmortem brain tissues, and yeast artificial chromosome (YAC) and C57B6/SJL transgenic positive (Tg+) mice overexpressing amyloid beta precursor protein (AβPP). In situ hybridization using mitochondrial DNA (mtDNA) probes for human wild type, 5 kb deleted, and mouse mtDNA was performed, along with immunocytochemistry using antibodies against amyloid precursor protein (APP), 8‐hydroxy‐2′‐guanosine (8‐OHG), and cytochrome c oxidase (COX). There was a higher degree of amyloid deposition in the vascular walls of the human AD, YAC, and C57B6/SJL Tg (+) mice compared to age‐matched controls. In addition, vessels with more severe lesions showed immunopositive staining for APP and possessed large, lipid‐laden vacuoles in the cytoplasm of endothelial cells (EC). Significantly more mitochondrial abnormalities were seen in human AD, YAC, and C57B6/SJL Tg (+) mouse microvessels where lesions occurred. In situ hybridization using wild and chimera (5 kb) mtDNA probes revealed positive signals in damaged mitochondria from the vascular endothelium and in perivascular cells of lesioned microvessels close to regions of large amyloid deposition. These features were absent in undamaged regions of human AD tissues, YAC and C57B6/SJL Tg (+) mouse tissues, and in age‐matched control subjects. In addition, vessels with atherosclerotic lesions revealed endothelium and perivascular cells possessing clusters of wild and deleted mtDNA positive probes. These mtDNA deletions were accompanied by increased amounts of immunoreactive APP, 8‐OHG, and COX in the same cellular compartment. Our observations demonstrate that vascular wall cells, especially their mitochondria, appear to be a central target for oxidative stress‐induced damage.
Systemic Effects of Dietary n‐3 PUFA Supplementation Accompany Changes of CNS Parameters in Cerebral Hypoperfusion
Authors: FARKAS ESZTER , de WILDE MARTIJN C. , KILIAAN AMANDA J. , LUITEN PAUL G. M.
Published: July 2009

Abstract: Dietary supplementation with long‐chain polyunsaturated fatty acids (PUFAs) has become an attractive possibility to alleviate or prevent cerebrovascular pathophysiology. To characterize the potentially beneficial cerebrovascular action of n‐3 PUFAs that predominantly occur in fish oil, we set up an experimental paradigm where rats with chronic cerebral hypoperfusion were supplied with n‐3 PUFA‐enriched diets. Cerebral hypoperfusion was created by a permanent, bilateral occlusion of the common carotid arteries (2VO) of rats at the age of 4 months, with a survival of 3 months. Simultaneously, the rats were provided with experimental diets from the time of weaning until the termination of the experiments. The control diet was comparable to standard rat chow, while diet 1 contained additional n‐3 PUFAs and diet 2 was further enriched with structural phospholipids and neurotransmitter precursors. In summary, the data show that diet 2 improved spatial learning of 2VO rats in the Morris water maze. Both diet 1 and diet 2 augmented blood‐brain barrier parameters and increased the density of the M1‐type muscarinic cholinergic receptors in the hippocampus independent of the rate of cerebral perfusion. In addition to an overview of these results, changes that were supportive or accompaning those described in the CNS are also presented. Briefly, plasma corticosterone concentration was elevated most explicitly by 2VO, while the relative weight of the liver and spleen increased due to the diets. The data draw attention to changes not only in the CNS, but also in the periphery as a consequence of chronic supplementation with n‐3 PUFA‐enriched diets.
Neuropsychological Deficits in Older Stroke Patients
Authors: BALLARD CLIVE , STEPHENS SALLY , McLAREN ANDREW , WESNES KEITH , KENNY ROSE ANNE , BURTON EMMA , O'BRIEN JOHN , KALARIA RAJ
Published: July 2009

Abstract: This paper examines the frequency of CIND, the profile of early cognitive deficits in stroke patients, the differences in the profile of cognitive impairment in people with CIND and those with vascular dementia, and the MRI associations of CIND in older stroke patients.
Paraoxonase 1 192/55 Gene Polymorphisms in Alzheimer's Disease
Authors: DANTOINE THIERRY F. , DROUET MIREILLE , DEBORD JEAN , MERLE LOUIS , COGNE MICHEL , CHARMES JEAN‐PIERRE
Published: July 2009

Abstract: An esterase, paraoxonase 1 (PON1), protects against organophosphate neurotoxicity and decreases lipoprotein oxidation. Two polymorphisms of PON1 [192 (R or Q) and 55 (M or L)] exist and are associated with coronary artery disease. We have previously shown that serum PON1 activity (PON1a) is lower in vascular dementia (VaD) than in Alzheimer's disease (AD), suggesting that PON1a may distinguish VaD from AD. As PON1 polymorphism modifies PON1a, we determined 192 and 55 PON1 polymorphisms by sequence‐specific primer PCR in 64 healthy subjects (HS; mean age: 79.5 ± 6.3 years; 38 women) and in 72 patients (mean age: 80.2 ± 6.8 years; 51 women) undergoing cognitive evaluations. According to DSM‐IV/NINCDS/ADRDA/NINDS/AIREN criteria, 45 patients (mean age: 80.0 ± 7.2 years, 34 women) had AD and 27 patients (mean age: 79.8 ± 6.6 years, 16 women) had VaD. We also measured serum PON1a by spectrophotometry. No significant differences in phenotype distributions among the three study groups were detected by χ2 test. Among the variables, age, sex, and phenotypes 192 and 55, logistic regression selected only polymorphism 192, but not 55, as a discriminating factor between AD and VaD (p < 0.05). Substitution of serum PON1a for genotype yielded a similar result. PON1 polymorphism 192 appears to be a reliable marker to distinguish patients with AD from patients with VaD and from healthy subjects. Changes in 192 polymorphism distributions in AD and in VaD may at least partially explain the significant difference in PON1a in these two types of dementia.
β‐Amyloid Fragment 25–35 Selectively Damages Platelets from Patients with Alzheimer's Disease
Authors: CASOLI TIZIANA , DI STEFANO GIUSEPPINA , DELFINO ALESSIA , SOLAZZI MORENO , FATTORETTI PATRIZIA , BERTONI‐FREDDARI CARLO , GUIDI MARCO , SCARPINO OSVALDO , GIUNTA SERGIO , GALEAZZI LUCIANO
Published: July 2009

Abstract: In order to analyze the metabolic response of AD patient platelets to β‐amyloid, we have carried out fluorimetric measurements of intracellular calcium and an ultrastructural survey of platelets exposed to the β‐amyloid active fragment 25–35 (βA25‐35). Since it is not possible to analyze directly the damaged neurons in AD, the study of peripheral blood cells, especially platelets, may be of great value for the investigation of the toxic effects of β‐amyloid on AD neuronal cells.
Cognitive Associations of Subcortical White Matter Lesions in Older People
Authors: O'BRIEN JOHN T. , WISEMAN REBECCA , BURTON EMMA J. , BARBER BOB , WESNES KEITH , SAXBY BRIAN , FORD GARY A.
Published: July 2009

Abstract: Hyperintense lesions (HL), as visualized on T2‐weighted or FLAIR MRI, are a common finding in older people, but their clinical significance and influence on cognitive function remain to be clarified. We investigated the relationship between HL in deep white and gray matter structures and cognition in older subjects. We recruited 154 nondemented (Mini‐Mental State Examination > 24) subjects (79 males) over the age of 70 from primary care (103 subjects with mild hypertension and 51 normotensive subjects). All subjects underwent FLAIR and proton density and T2‐weighted axial 1.5‐tesla MRI scans (slice thickness: 5 mm). The scans were rated for the presence and distribution of HL in the subcortical gray matter (caudate, putamen, globus pallidus, thalamus) and associated white matter tracts (internal/external capsule). Subjects (n= 149) underwent a comprehensive cognitive assessment involving tests of attention, processing speed, episodic memory, working memory, and executive function. Partial correlations (correcting for age, systolic blood pressure, and New Adult Reading Test [NART] score) were performed to investigate the relationship between cognition and white matter change. HL were found in 49% of subjects. HL in both the gray (thalamus and caudate) and white matter were significantly associated with impaired cognitive function in tasks involving processing speed and/or executive function, but showed no associations with episodic or working memory. HL in both subcortical gray matter structures and associated fiber tracts correlate with impairments in attention, executive function and processing, and memory retrieval speed in nondemented older community‐dwelling subjects. Such lesions may be an important cause of age‐related attentional and executive dysfunction in the elderly, as well as temporal lobe and hippocampal changes that have previously been reported to be associated with impairments to the ability to actually store and retrieve information from memory.
Acetazolamide Vasoreactivity in Vascular Dementia and Persistent Vegetative State Evaluated by Transcranial Harmonic Perfusion Imaging and Doppler Sonography
Authors: SHIOGAI T. , UEBO C. , MAKINO M. , MIZUNO T. , NAKAJIMA K. , FURUHATA H.
Published: July 2009

Abstract: To clarify the pathophysiological differences of the cerebrovascular reserve capacity in relation to cerebral cognitive impairments between vascular dementia (VaD) and persistent vegetative state (PVS), we evaluated acetazolamide (ACZ) vasoreactivity testing by transcranial harmonic perfusion imaging (HPI) and Doppler sonography (TCD). Sixteen patients (age: 29–85 years; mean: 62) were divided into three groups: 7 VaD, 4 PVS, and 5 nondementia patients. Mean velocity (Vm) in the middle and posterior cerebral artery (MCA, PCA) was measured, and time‐intensity curves of the HPI were evaluated at three regions of interest—the bilateral temporal lobe (TL), basal ganglia (BG), and thalamus (Th). TCD and HPI were evaluated before (resting state) and after ACZ administration, and vasoreactivity was compared among the three groups in terms of resting values and relative changes (%Δ) of Vm, peak intensity (PI), area under curve (AUC), and mean transit time (MTT). Results of the resting state: Decreased Vm, PI, and AUC of the VaD and PVS groups were more obvious in the right side. Results of vasoreactivity: In the PVS group, %ΔVm decreased in the left PCA and MCA; %ΔPI and %ΔAUC decreased in the left TL and bilateral BG. In the VaD group, %ΔPI and %ΔAUC decreased in the right TL; %ΔMTT tended to increase in the left side. ACZ vasoreactivity tests by transcranial HPI and TCD allowed bedside, noninvasive quantitative evaluation of the pathophysiology of cognitive function impairment in relation to cerebrovascular reserve capacity in VaD and PVS.
Lymphatic Vessel Activation in Cancer
Authors: CASSELLA MELANIE , SKOBE MIHAELA
Published: July 2009

Abstract: Metastasis of most cancers occurs primarily through the lymphatic system, and the extent of lymph node involvement is the most important prognostic indicator. While the importance of the lymphatic system as a pathway for metastasis has been well recognized, there is very little information available about the mechanisms by which tumor cells interact with the lymphatics. Recently, production of the lymphangiogenic factor VEGF‐C has been detected in tumors, and the significance of VEGF‐C‐mediated lymphangiogenesis for tumor metastasis has been demonstrated. Increased lymphatic vessel density has been found associated with certain tumors. The mechanisms by which tumor cells gain access to and enter lymphatic vessels are critical issues that need to be addressed in the future. In contrast to the prevailing view that has assigned to the lymphatic system a passive role in the metastatic process, our results indicate the importance of lymphatic vessel activation in tumor dissemination.
The Molecular Control of Adipogenesis, with Special Reference to Lymphatic Pathology
Authors: ROSEN EVAN D.
Published: July 2009

Abstract: Adipogenesis is the process by which mature fat cells are formed from pre‐adipocytes. Adipogenesis has come under increasing scrutiny not only because the availability of reliable in vitro models makes it an attractive choice for developmental studies, but also because adipocytes are increasingly recognized as major players in a variety of physiological and pathophysiological states, such as obesity and type 2 diabetes. Adipocytes develop from mesenchymal stem cell precursors that are characterized by multipotency. Under the influence of various cues, these cells become committed to the adipocyte lineage. Further hormonal stimulation recruits these pre‐adipocytes to accumulate lipid, express fat‐specific markers, and become sensitive to the metabolic effects of insulin. A complex transcriptional cascade regulates this process, involving several distinct classes of transcription factor. In particular, the role of the nuclear hormone receptor PPARγ will be discussed, along with bZip family members C/EBPα, C/EBPβ, and C/EBPδ. The relationship of adipose depots to the lymphatic system will also be discussed.
Physiologic Aspects of Lymphatic Contractile Function
Authors: GASHEV ANATOLIY A.
Published: July 2009

Abstract: The lymphatic system plays an important role in fluid/macromolecular balance, lipid absorption, and immune functions, and is involved in many different pathologic conditions, like inflammation, spread of cancer cells, and lymphedema. There are several forces that drive lymph centripetally. Extrinsic driving forces, or the passive lymph pump, include lymph formation, arterial pulsations, skeletal muscles contractions, fluctuations of central venous pressure, gastrointestinal peristalsis, and respiration. Intrinsic forces, or the active lymph pump, are the result of coordinated contractions of lymphangions, the morpho‐functional units of the lymphatic vessels, which include the valve and portion of the vessel extending to the next valve. The contractions of the lymphangions are initiated by the pacemaker activity of the smooth muscle cells of lymphangion wall. Transmural pressure is an important hydrodynamic factor that modulates pacemaking. Under conditions of low filling, lymphangions might produce negative intraluminal pressures and a suction effect. Because of the complicated hydrodynamic conditions in lymphatic beds, the passive and active lymph pumps sometimes work together to propel lymph centripetally. In other cases (i.e., under conditions of enhanced lymph flow), flow‐mediated inhibition of the active lymph pump could serve to decrease lymphatic outflow resistance and save metabolic energy when the driving force of the passive lymph pump is enough to propel lymph. We have recently found that there are profound differences in the pressure and flow sensitivities of lymphatic vessels derived from different tissues, such as the thoracic duct and mesenteric lymphatics. Such results, when considered in light of the controversy surrounding some studies performed in different animals, lead to the idea that the active lymph pumps in humans may have greater regional differences in contractile function than has been seen in animals, because of the upright posture in bipedal humans. This posture creates an additional outflow resistance for lymphatics of the lower part of the body. Thus, despite the ongoing attempts to determine the mechanisms of lymphatic diseases and useful therapies to treat them, there are many disputable or unknown issues regarding the physiology of lymph transport in humans.
Tumor Hypoxia and Blood Vessel Detection
Authors: LOUKAS CONSTANTINOS G. , WILSON GEORGE D. , VOJNOVIC BORIVOJ , LINNEY ALF
Published: July 2009

Abstract: We have developed a multistage image analysis technique for the simultaneous segmentation of blood vessels and hypoxic regions in dual‐stained tumor tissue sections. The algorithm, which is integrated in a task‐oriented image analysis system developed on‐site, initially uses the K‐nearest neighbor classification rule in order to label the image pixels. Classification is based on a training set selected from manually drawn regions corresponding to the areas of interest. If the output image contains a significant number of misclassified pixels, the user has the option to apply a series of specific problem‐designed routines (texture analysis, fuzzy c‐means clustering, and edge detection) in order to improve the final segmentation result. Validation experiments indicate that the algorithm can robustly detect these biological features, even in tissue sections with a very low quality of staining. This approach has also been combined with other image analysis based procedures in order to objectively obtain quantitative measurements of potential clinical interest.
Compression and Filtration of U.S. Medical Images with a Modified Inverse Difference Pyramid
Authors: MILANOVA MARIOFANNA , KOUNTCHEVA ROUMIANA , RUBIN STUART , TABRIZI MOHAMMAD
Published: July 2009

Abstract: In this paper a new approach for compression and filtration of U.S. medical images is introduced. The application of the algorithm, based on image processing with an inverse difference pyramid (IDP) along with considerable image compression, permits filtration of a specific (speckle) noise in ultrasound images. The paper describes the principle of image decomposition and its modification designed specifically for this medical application. The paper also provides images that illustrate some of the results of this work.
Designing a Patient Education Framework via Use Case Analysis
Authors: DIONISIO JOHN DAVID N. , BUI ALEXANDER A.T. , JOHNSON DAVID B. , THOMPSON LYNN L. , SINHA USHA
Published: July 2009

Abstract: One of the challenges of developing patient education content in electronic form is to determine the information and interaction needs that motivate a patient to learn in the first place. We have found that use case analysis of patient education helps in clarifying the types of information and interaction required to educate a patient effectively. This paper presents a use case model for patient education as well as a Java‐based framework that facilitates both the extension and updating of individually tailored, electronic patient education content. The framework defines an abstract interface that represents a particular panel of information, and provides a content manager that dynamically discovers and refreshes new panels as they are added or modified.