bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation of Neuroendocrine Chromaffin Cells from Sympathoadrenal Progenitors
Authors: HUBER KATRIN , COMBS STEPHANIE , ERNSBERGER UWE , KALCHEIM CHAYA , UNSICKER KLAUS
Published: July 2009

Abstract: The developmental diversification of neural crest‐derived sympathoadrenal (SA) progenitor cells into neuroendocrine adrenal chromaffin cells and sympathetic neurons has been thought to be largely understood. Based on two decades of in vitro studies with isolated SA progenitor and chromaffin cells, it was widely assumed that chromaffin cell development crucially depends on glucocorticoid hormones provided by adrenal cortical cells. However, analysis of mice lacking the glucocorticoid receptor has revealed that the chromaffin cell phenotype develops largely normally in these mice, except for the induction of the adrenaline synthesizing enzyme phenylethylamine N‐methyl transferase. In a search for novel candidate genes that might be involved in triggering the sympathetic neuron/chromaffin cell decision, we have studied putative contributions of transforming growth factor (TGF)‐α, BMP‐4, and the transcription factor MASH‐1, molecules with distinct expressions in SA progenitor cells, in their migratory pathways and final destinations. TGF‐β2 and ‐β3 and BMP‐4 are highly expressed in the wall of the dorsal aorta and in the adrenal anlagen during and after immigration of SA progenitors but expressed at much lower levels in sympathetic ganglia. We found that neutralizing antibodies against all three TGF‐β isoforms applied to the chorionic‐allantoic membrane (CAM) of quail embryos interfere with proliferation of immigrated adrenal chromaffin cells but do not affect their specific neuroendocrine ultrastructural phenotype. Grafting of noggin‐producing cells to the CAM, which scavenges BMPs, interferes with visceral arch and limb development but does not overtly affect the chromaffin phenotype. The transcription factor MASH‐1 promotes early differentiation of SA progenitors. Mice deficient for MASH‐1 lack sympathetic ganglia, whereas the adrenal medulla previously has been reported to be present. We show here that most adrenal medullary cells in MASH‐1−/− mice identified by Phox2b immunoreactivity lack the catecholaminergic marker tyrosine hydroxylase. More surprisingly, most cells do not contain chromaffin granules and display a neuroblast‐like ultrastructure and show strongly enhanced expression of c‐RET comparable to that observed in sympathetic ganglia. Together, our data suggest that TGF‐βs and BMP‐4 do not seem to be essential for chromaffin cell differentiation. In contrast with previous reports, however, MASH‐1 apparently plays a crucial role in chromaffin cell development.
A New Green Fluorescent Protein Construct for Localizing and Quantifying Peptide Release
Authors: HAN WEIPING , LI DANQING , LEVITAN EDWIN S.
Published: July 2009

Abstract: Green fluorescent protein (GFP)‐tagged secretory proteins recently have been used for studying packaging of peptides, secretory vesicle dynamics, and regulation of peptide release. In cells in which release occurs from sites with an abundance of vesicles, it is difficult to resolve the exact location of individual exocytotic events with standard wide‐field epifluorescence microscopy. Furthermore, current GFP constructs are not well suited for real‐time measurement of peptide release from large numbers of cells. Here, we describe a new pH‐sensitive construct that is designed for localizing and quantifying release of neuropeptides and peptide hormones. Specifically, the yellow GFP variant called Topaz was fused to proAtrial natriuretic peptide (proANP, also called proAtrial natriuretic factor). The fluorescence of this fusion protein is low in normally acidic secretory vesicles but increases approximately 10‐fold upon neutralization. Furthermore, it is released upon depolarization of PC12 cells. Finally, individual release events can be detected as brief localized flashes of fluorescence. ProANF‐Tpz should prove useful for studying single release events by wide‐field epifluorescence microscopy and for fluorometer‐based real‐time peptide release measurements from high numbers of cells.
Image Flows and One‐Liner Graphical Image Representation
Authors: MAKHERVAKS VADIM , BAREQUET GILL , BRUCKSTEIN ALFRED
Published: July 2009

Abstract: This paper introduces a novel graphical image representation consisting of a single curve—the one‐liner. The first step of the algorithm involves the detection and ranking of image edges. A new edge exploration technique is used to perform both tasks simultaneously. This process is based on image flows. It uses a gradient vector field and a new operator to explore image edges. Estimation of the derivatives of the image is performed by using local Taylor expansions in conjunction with a weighted least‐squares method. This process finds all the possible image edges without any pruning, and collects information that allows the edges found to be prioritized. This enables the most important edges to be selected to form a skeleton of the representation sought. The next step connects the selected edges into one continuous curve—the one‐liner. It orders the selected edges and determines the curves connecting them. These two problems are solved separately. Since the abstract graph setting of the first problem is NP‐complete, we reduce it to a variant of the traveling salesman problem and compute an approximate solution to it. We solve the second problem by using Dijkstra's shortest‐path algorithm. The full software implementation for the entire one‐liner determination process is available.
Photogrammetric and Image Processing Aspects in Quantitative Flow Visualization
Authors: MACHACEK MATTHIAS , RÖSGEN THOMAS
Published: July 2009

Abstract:The development of a measurement system for the visualization, topological classification, and quantitative analysis of complex flows in large‐scale wind tunnel experiments is described. A new approach was sought in which the topological features of the flow (e.g., stream lines, separation and reattachment regions, stagnation points, and vortex lines) were extracted directly and preferably visualized in real‐time in a virtual wind tunnel environment. The system was based on a stereo arrangement of two CCD cameras. A frame rate of 120 fps allowed measurements at high flow velocities. The paper focuses on the problem of fast and accurate reconstruction of path lines of helium filled soap bubbles in three dimensions (3D). A series of simple algorithmic steps was employed to ensure fast data processing. These included fast image segmentation, a spline approximation of the path lines, a camera model, point correspondence building, calculation of path line points in 3D and creation of a three‐dimensional spline representation. The path lines, which contained both velocity and topological information, were analyzed to extract the relevant information.
Vortex Scale of Unsteady Separation on a Pitching Airfoil
Authors: FUCHIWAKI MASAKI , TANAKA KAZUHIRO
Published: July 2009

Abstract: The streaklines of unsteady separation on two kinds of pitching airfoils, the NACA65‐0910 and a blunt trailing edge airfoil, were studied by dye flow visualization and by the Schlieren method. The latter visualized the discrete vortices shed from the leading edge. The results of these visualization studies allow a comparison between the dynamic behavior of the streakline of unsteady separation and that of the discrete vortices shed from the leading edge. The influence of the airfoil configuration on the flow characteristics was also examined. Furthermore, the scale of a discrete vortex forming the recirculation region was investigated. The non‐dimensional pitching rate was k= 0.377, the angle of attack αm= 16° and the pitching amplitude was fixed to A=±6° for Re= 4.0 × 103 in this experiment.
Imaging the Transient Boundary Layer on a Free Rotating Disc
Authors: MATIJAŠEVIĆ BRANIMIR , GUZOVIĆ ZVONIMIR , MARTINIS VINKO
Published: July 2009

Abstract: This report presents a visual study of the transition process of the laminar boundary layer (BL) in a turbulent BL on a free rotating disc. The imaging is based on an experimental investigation that aimed to analyze the structure of the BL by relating it to the ratio between turbulent energy and vortex energy, the critical and the transient Reynolds numbers (Re), the vortex numbers and their dependence on Re, and on the distance from the rotating disc.
Development and Validation of an X‐ray Tomograph for Two‐Phase Flow
Authors: HERVIEU ERIC , JOUET EMMANUEL , DESBAT LAURENT
Published: July 2009

Abstract: This paper describes the development and validation of a high spatial resolution X‐ray tomograph designed for the investigation of air‐water two‐phase flow. The device hardware mainly comprises a 60 keV X‐ray source, a detector, and an accurate mechanical bench. Our study concentrated on accurate quantification with emphasis on the reconstruction procedure. As is well known, absorption gradients induce reconstruction artifacts when using standard algorithms based on uniform regularization. In the particular case of two‐phase flow in a pipe, this leads to poor measurement accuracy in the vicinity of the walls. To overcome such effects, improved algorithms were developed during this study that involve spatially adaptive regularization methods. Preliminary calibration performed on static phantoms clearly exhibited the benefits of the advanced reconstruction algorithms. A validation procedure was carried out on an air‐water bubble column, equipped with an optical probe, which could be translated in order to explore the 80 mm × 80 mm square cross section. Comparisons of local void fraction measurements were performed pixel by pixel. They demonstrate the accuracy improvement induced by the advanced reconstruction algorithms.
Neutrophils Movement in Vitro
Authors: KORZYŃSKA ANNA
Published: July 2009

Abstract: Ineffectiveness of the motility of neutrophils is observed in some immunodeficiency disorders. There is a need to find an adequate description and means to evaluate the activity of neutrophils. Early studies describe an individual cell behavior by the cell motility index vector with three components: penetration, directionality, and expansivenesses. Movement quantification has been improved by extending the description of cell activity to two stages of classification. In the first stage, one minute of each cell's behavior is classified into one of five types of cell behavior, using the k‐NN method. In the second stage, the sample level that corresponds to the final classification, the Shapiro‐Francio test has been used. The proposed new method allows us to describe differences between a normal child and a Chediak‐Higashi syndrome patient.
An Algorithm for Estimating Chaos in Mechanoemission of Blood and Magnetic Resonance Imaging in Patients with Gastric Cancer
Authors: OREL VALERIY E. , ROMANOV ANDREY V. , DZYATKOVSKAYA NATALIE N. , MEL'NIK YURI I.
Published: July 2009

Abstract: The paper describes an algorithm and computational system used to estimate the spatial chaos of magnetic resonance images of patients with gastric cancer and the quantum chaos of mechanoemission in blood.
Temperature and Flow Visualization in a Simulation of the Czochralski Process Using Temperature‐Sensitive Liquid Crystals
Authors: ALEKSIC JELENA , ZIELKE PAUL , SZYMCZYK JANUSZ A.
Published: July 2009

Abstract: There is no doubt today that thermal and thermocapillary convection play a dominant role in momentum, heat, and mass transfer in the Czochralski crystal growth method. Because of the complexity of the problems, measurements in one point of the volume are not sufficient to illuminate the flow topography or to compare the experimental results with real or numerically simulated data. Therefore, it is of great interest to measure the temperatures and velocities in the whole field in order to qualitatively analyze thermally driven convection. The new experimental particle image thermometry method, based on computer‐aided color analysis of the TLCs reported here, enables the simultaneous determination of the temperature and velocity fields.
Unsteady Flow Patterns in the Vicinity of Heated Wall‐Mounted Transverse Ribs
Authors: POLIDORI GUILLAUME , PADET JACQUES
Published: July 2009

Abstract: This paper deals with experimental modeling of the unsteady junction flow features in the vicinity of an isoflux heated wall with mounted insulated rectangular ribs representing three distinctive ribbed test geometries. Both flow visualizations and surface temperature distributions show that the blockage effect upstream of the ribs, as well as the presence of complex eddy structures inside the open cavities, significantly affect the heat transfer process. All the configurations indicate degraded heat transfer performance in the area close to the ribs and an enhancement just downstream from the last rib.
Renal Handling of X‐ray Contrast Media Imaging and Exploration with Electron Beam CT
Authors: RULE ANDREW D. , BAJZER ŽELJKO , RITMAN ERIK L. , LERMAN LILACH O.
Published: July 2009

Abstract: Physiologic changes in renal hemodynamics and function reflect its role as a regulatory organ in maintaining homeostasis, whereas other alterations may mirror development of renal injury and often precede overt signs of morphologic changes. Furthermore, intrarenal alterations may be discreet and manifest only in the renal cortical, medullary, or papillary zones. The high spatial and temporal resolution of electron‐beam computed tomography enables external detection and quantification of cortical, medullary, and papillary tissue density changes following an intravenous bolus injection of X‐ray contrast media. These changes reflect flow of contrast media in these renal zones through the successive renal vascular, glomerular, and tubular compartments that can be individually plotted as time‐density curves (TDC). Mathematical modeling then allows calculation of unique parameters of renal function from these TDC. This ability to quantify renal regional attributes may not only shed light on the physiologic mechanisms that the kidney controls, but also assist in detecting subtle impairment in its function.
Exposure of Human Skin Diploid Fibroblasts to Repeated Subcytotoxic Doses of Ultraviolet‐B Induces the Overexpression of Transforming Growth Factor‐β1 mRNA
Authors: CHAINIAUX FLORENCE , REMACLE JOSÉ , TOUSSAINT OLIVIER
Published: July 2009

Abstract: In this work we show that the steady state mRNA level of TGF‐β1 is significantly increased in UVB‐induced premature senescence.
Signaling Pathways Mediate the Neuroprotective Effects of GDNF
Authors: NEFF F. , NOELKER C. , EGGERT K. , SCHLEGEL J.
Published: July 2009

Abstract: We show that the glial cell line‐derived neurotrophic factor (GDNF) activates the PI3K/Akt‐signaling pathway in human neuroblastoma cells that express functional Ret‐receptor complexes. Consistent with this finding we show PI3K‐dependent Bad‐inactivation by binding to 14‐3‐3 proteins in response to GDNF. Using differential display techniques we detected several cDNA clones differentially expressed after treatment with GDNF or 6‐OHDA.
The Activity of the Insulin Receptor Assessed by Bioluminescence Resonance Energy Transfer
Authors: ISSAD TARIK , BOUTE NICOLAS , PERNET KARINE
Published: July 2009

Abstract:This work describes a new assay, based on the bioluminescence resonance energy transfer (BRET) methodology, to monitor the activation state of the insulin receptor.
Decorin Affects Endothelial Cells by Akt‐Dependent and ‐Independent Pathways
Authors: SCHÖNHERR E. , LEVKAU B. , SCHAEFER L. , KRESSE H. , WALSH K.
Published: July 2009

Abstract: Decorin, a small multifunctional proteoglycan, has been shown to be causally involved in the formation of capillary‐like structures and a decrease in apoptosis. Here we investigated signal transduction pathways mediating effects of decorin on endothelial cells (ECs). Addition of decorin led to a fourfold increase in phosphorylation of Akt/protein kinase B on Thr307 and a l.4‐fold increase on Ser473 after 10 min, but this phosphorylation could not be blocked by preincubation with Ly29400 (10 μM). Six hours after the addition of decorin, the synthesis of p21 and p27, two inhibitors of cyclin‐dependent kinases, started and increased up to 18 h, while synthesis of cyclin A peaked at 12 h and decreased after 24 h below base level. Induction of dominan‐negative Akt by a replication‐deficient adenovirus blocked p21 and cyclin A synthesis, but had no effect on p27. Dominant‐negative Akt also blocked the antiapoptotic effect of decorin on ECs, but induction of dominant‐positive Akt could not rescue the cells from apoptosis. Thus, the matrix proteoglycan decorin is a signaling molecule in ECs that affects cell survival by Akt‐dependent and ‐independent pathways.
The Role of Mitogen‐Activated Protein Kinases and Their Relationship with NF‐κB and PPARγ in Indomethacin‐Induced Apoptosis of Colon Cancer Cells
Authors: KIM TAE IL , JIN SOO HYUN , KANG EUN HYE , SHIN SUNG KWAN , CHOI KANG YELL , KIM WON HO
Published: July 2009

Abstract: We have evaluated the role of mitogen‐activated protein kinases (MAPKs) and their relationship with nuclear factor κB (NF‐κB) and peroxisome proliferator‐activated receptor γ (PPARγ) in indomethacin‐induced apoptosis of colon cancer cells. We demonstrated that indomethacin can induce the prolonged activation of MAPKs in colon cancer cells; and that of these MAPKs, p38 MAPK may play a partial but significant role in indomethacin‐induced apoptosis. Furthermore, indomethacin‐induced p38 MAPK‐mediated apoptosis of colon cancer cell lines is independent of caspase activation and not associated with indomethacin‐induced NF‐κB suppression and PPARγ activation.
Nucleolus and Apoptosis
Authors: HORKÝ M. , KOTALA V. , ANTON M. , WESIERSKA‐GADEK J.
Published: July 2009

Abstract: The nucleolus represents a highly dynamic nuclear compartment of the interphase nucleus. It plays a key role in ribosome biogenesis. The number of nucleoli, their size, and their activity increase in exponentially growing cells; therefore these parameters reflect the proliferating activity of the cells. A variety of staining techniques have been employed to vizualize nucleolar changes in malignant cells. Staining of so‐called nucleolar organizer regions (NORs), based upon a strong avidity of nucleolar proteins to bind silver ions, represents the technique most frequently used by pathologists. Nucleolar changes and pleomorphism associated with overt proliferation of tumor cells have also been documented by immunohistochemical and ultrastructural studies. Contrary to cell proliferation, cytostatics‐induced changes of nucleolar phenotype in malignant cells point to a potential role of nucleolar components in the execution of active cell death. Recent studies have provided direct clues that so‐called death domains and other apoptosis‐related proteins are accumulated in nucleoli upon induction of active cell death. It can be concluded that the plurifunctionality of nucleoli regarding cell proliferation and apoptosis could open new vistas toward understanding dysregulation in malignant cells.
Dynamic Localization/Association of Protein Kinase CK2 Subunits in Living Cells
Authors: MARTEL VÉRONIQUE , FILHOL ODILE , NUEDA ARSENIO , COCHET CLAUDE
Published: July 2009

Abstract: Accumulating evidence indicates that in addition to the classical complex, the catalytic and regulatory subunits of CK2 can also exist as free populations in living cells. The association of recombinant CK2 subunits in vitro has been characterized, providing evidence for the first time for their targeted interactions in living cells. The data also suggest that the regulation by phosphorylation of many CK2 substrates may strongly depend on the dynamic localization/association of its subunits.
From Extracellular to Intracellular Targets, Inhibiting MAP Kinases in Treatment of Crohn's Disease
Authors: VAN DEN BLINK BERNT , ten HOVE TESSA , VAN DEN BRINK GIJS R. , PEPPELENBOSCH MAIKEL P. , VAN DEVENTER SANDER J.H.
Published: July 2009

Abstract:In recent years the emphasis in finding new therapeutic options for chronic inflammatory diseases has been on targeting extracellular mediators of inflammation. A range of tools has become available to interfere with signaling by cytokines and their receptors. As our understanding of the intracellular pathways that mediate inflammatory signals expands, new therapeutic targets within the inflammatory cells come into sight. In this review we will discuss possible intracellular targets for treatment in Crohn's disease, a chronic relapsing inflammatory disease of the gut. Despite the encouraging results with anti‐TNF antibodies in patients with Crohn's disease, our current treatment options are still insufficient and warrant novel treatment strategies. The mitogen‐activated protein kinase (MAPK) family of signal transduction proteins is an important intracellular mediator of inflammation, and recently a MAPK inhibitor was successfully used in patients with Crohn's disease. We will discuss our current understanding of the molecular pathophysiology of Crohn's disease and also novel therapies that specifically target members of the MAPK pathway.
Multiple Degradation Pathways for Fos Family Proteins
Authors: ACQUAVIVA CLAIRE , BOSSIS GUILLAUME , FERRARA PATRIZIA , BROCKLY FRÉDÉRIQUE , JARIEL‐ENCONTRE ISABELLE , PIECHACZYK MARC
Published: July 2009

Abstract: c‐Fos protooncoprotein is a short‐lived transcription factor with oncogenic potential. It is massively degraded by the proteasome in vivo under various experimental conditions. Those include consititutive expression in exponentially growing cells and transient induction in cells undergoing the G0/G1 phase transition upon stimulation by serum. Though there is evidence that c‐Fos can be ubiquitinylated in vitro, the unambigous demonstration that prior ubiquitinylation is necessary for degradation by the proteasome in vivo is still lacking. c‐Jun, one of the main dimerization partners of c‐Fos within the AP‐1 transcription complex, is also an unstable protein. Its degradation is clearly proteasome dependent. However, several lines of evidence indicate that the mechanisms by which it addresses the proteasome are different from those operating on c‐Fos. Moreover, genetic analysis has indicated that c‐Fos is addressed to the proteasome via pathways that differ depending on the conditions of expression. c‐Fos has been transduced by two murine osteosarcomatogenic retroviruses in mutated forms, which are more stable and more oncogenic. The stabilization is not simply accounted for by simple deletion of one of the main c‐Fos destabilizers but, rather, by a complex balance between opposing destabilizing and stabilizing mutations. However, although viral Fos proteins have acquired full resistance to proteasomal degradation, stabilization is limited because the mutations they have accumulated, during or after c‐fos gene transduction, confer sensitivity to an unidentified proteolytic system(s). This observation is consistent with the idea that fos‐expressing viruses have evolved expression machineries to ensure controlled protein levels in order to maintain an optimal balance between prooncogenic and proapoptotic activities of v‐Fos proteins.
Cyclooxygenase‐2 Expression by Transcription Factors in Helicobacter pylori‐Infected Gastric Epithelial Cells: Comparison between HP 99 and NCTC 11637
Authors: SEO JI HYE , KIM HYEYOUNG , KIM KYUNG HWAN
Published: July 2009

Abstract: Helicobacter pylori, a gram‐negative spiral bacterium, has been associated with chronic gastritis and gastric cancer. HP 99, isolated from the Korean patients, and NCTC 11637, obtained from ATCC, have different genotypes. The present study aims to investigate whether these H. pylori strains show the discrepancy for activating transcription factors (NF‐κB, AP‐1, C/EBP) and induction of cyclooxygenase‐2 (COX‐2) gene in gastric epithelial AGS cells. After treatment of H. pylori to AGS cells at the ratio of 300:1, the activation of transcription factors was assessed by electrophoretic mobility shift assay. COX‐2 protein was determined by Western blot analysis. The level of 6‐keto‐prostaglandin F1α (6‐keto‐PGF1α), a COX‐2 product, was measured in the medium by enzyme‐linked immunosorbent assay. As a result, both H. pylori strains similarly induced COX‐2 expression via activation of NF‐κB, not C/EBP, and increased the level of 6‐keto‐PGF1α. HP 99 showed much higher activation of AP‐1 compared to NCTC 11637. NF‐κB might play an important role in COX‐2 expression in H. pylori‐induced gastric inflammation as compared to other transcription factors.
Contribution of Covalent Protein Modification to the Antiinflammatory Effects of Cyclopentenone Prostaglandins
Authors: PÉREZ‐SALA DOLORES , CERNUDA‐MOROLLÓN EVA , PINEDA‐MOLINA ESTELA , CAÑADA F. JAVIER
Published: July 2009

Abstract: Cyclopentenone prostaglandins, which are produced during inflammatory processes, may exert a negative feedback on inflammation. These reactive compounds may form covalent adducts with thiol groups in glutathione or in proteins. The transcription factor NF‐κB is key for the expression of numerous proinflammatory genes. We have observed that treatment of mesangial cells with 15‐deoxy‐Δ12,14‐prostaglandin J2 (15d‐PGJ2) inhibits the cytokine‐elicited DNA binding activity of NF‐κB, both in intact cells and in isolated nuclear extracts, thus suggesting a direct effect on DNA binding. By using a biotinylated 15d‐PGJ2 derivative, we have observed that 15d‐PGJ2 forms an adduct with the p50 subunit of NF‐κB, as shown by Western blot and detection with horseradish peroxidase‐conjugated streptavidin. In contrast, a p50 construct that bears a mutation in the cysteine residue involved in DNA binding (Cys62Ser) and is not susceptible to inhibition by 15d‐PGJ2 does not incorporate biotinylated 15d‐PGJ2. The labeling of several polypeptides after incubation of cells with biotinylated 15d‐PGJ2 suggests that there may be multiple targets for modification by 15d‐PGJ2. We propose that the covalent modification of NF‐κB (and potentially other proteins) by 15d‐PGJ2 may contribute to the antiinflammatory effects of this prostaglandin.
Regulation of the Metastatic Process by E‐Selectin and Stress‐Activated Protein Kinase‐2/p38
Authors: LAFERRIÈRE JULIE , HOULE FRANÇOIS , HUOT JACQUES
Published: July 2009

Abstract: The formation of metastasis is a dreadful complication of cancer that is associated with a poor prognosis. Several clinical observations and experimental findings indicate that the metastatic process is nonrandom and involves a sequence of multistep events that may all be targeted for therapy. This includes angiogenesis of the primary neoplasm, release of malignant cells from this neoplasm, entry of cancer cells into the blood circulation, interaction of cancer cells with vascular endothelial cells in distant organs, and growth of blood‐borne cancer cells locally in the vessels or distally following extravasation. Our working hypothesis is that metastatic cancer cells exploit the mechanisms of the inflammation process to successfully migrate into distant organs. This implies a pivotal role for specific adhesive interactions between cancer cells and vascular endothelial cells and activation of migratory pathways in the cancer cells. We review here the roles played by the endothelial adhesive molecule E‐selectin and by the motogenic stress‐activated protein kinase‐2 (SAPK2/p38) pathway of cancer cells in modulating transendothelial migration of cancer cells.
Incidence and Risk Factors of Dementia in a Defined Elderly Japanese Population
Authors: FUJISHIMA MASATOSHI , KIYOHARA YUTAKA
Published: July 2009

Abstract: Vascular dementia (VaD) is more common than Alzheimer's disease (AD) in Japan, while AD is much more frequent in Western countries. The Hisayama study, an epidemiological study on dementia in a Japanese elderly population aged 65 years or older, has shown that the prevalence of VaD decreased for men, while AD remained unchanged in both sexes during a 7‐year follow‐up period (1985‐1992). Decreased prevalence of VaD seems to be due to decreased incidence of stroke in recent years, resulting from the management of hypertension. The age‐adjusted incidence of total dementia was approximately 20 per 1000 person‐years in either sex; VaD was more frequent for men and AD for women. Risk factors for VaD were age, hypertension, previous stroke, and alcohol consumption, while age was only a significant risk factor for AD. Although the Hisayama study failed to demonstrate the relationship of vascular factors to AD, the previously reported studies suggest that either hypertension per se or blood pressure changes appear to partially participate in the pathogenesis of AD.
Vascular Dementia in Japan
Authors: YANAGIHARA TAKEHIKO
Published: July 2009

Abstract: Patients with vascular dementia are frequently encountered in Japan reaching nearly 50% of those with senile dementia, which is equal to or even slightly higher than patients with Alzheimer's disease. This contrasts with a much lower ratio of patients with vascular dementia in the United States. The majority of vascular dementia seen in Japan is of the multiple lacunar type or Binswanger disease, often without any episode of stroke. Clinically, those patients tend to have attention deficit and reduction of spontaneous activities. The observed characteristics of vascular dementia likely reflect the main type of cerebrovascular disease prevalent in Japan since the majority of cerebral infarction in Japan is of lacunar type in contrast to that in the United States and Europe. For patients without any episode of stroke, it is important to differentiate from Alzheimer's disease. As in the United States and Europe, mixed dementia exists in Japan with Alzheimer's disease and vascular dementia together and poses problems in clinical diagnosis because many patients may not have any episode of stroke, but they have neuroimaging characteristics compatible with both. The number of patients with atherosclerosis in large cervical and cerebral arteries is said to be increasing in Japan, and vascular dementia in Japan may present with different clinical pictures in the future.
Hypertension and Related Factors in the Etiology of Alzheimer's Disease
Authors: SKOOG INGMAR , GUSTAFSON DEBORAH
Published: July 2009

Abstract: The prevalence of hypertension is estimated to approach 50% in individuals above age 70. The consequences of hypertension include cerebrovascular disease, coronary heart disease, and general atherosclerosis. Several recent studies suggest that there may be an association also between hypertension and Alzheimer's disease (AD). This review will examine the evidence for this association and possible pathways between hypertension, Alzheimer encephalopathy, and clinical dementia.
Proinflammatory and Vasoactive Effects of Aβ in the Cerebrovasculature
Authors: TOWNSEND K. P. , OBREGON D. , QUADROS A. , PATEL N. , VOLMAR Ch. , PARIS D. , MULLAN M.
Published: July 2009

Abstract: Aβ peptides are thought to be critical molecules in the pathophysiology of Alzheimer's disease (AD) and are the major protein constituents of senile plaques. In most AD cases, Aβ peptides also form some deposits in the cerebrovasculature, leading to cerebral amyloid angiopathy and hemorrhagic stroke. Regional cerebral hypoperfusion is one of the earlier clinical manifestations in both the sporadic and familial forms of AD. In addition, a variety of vascular risk factors of different etiologies (for instance, diabetes, hypertension, high cholesterol level, atherosclerosis, and smoking) constitute risk factors for AD as well, suggesting that functional vascular abnormalities may contribute to AD pathology. We studied the effect of Aβ on constrictor responses elicited by endothelin‐1 in isolated human cerebral arteries collected following rapid autopsies. We report that freshly solubilized Aβ potentiates endothelin‐1‐induced vasoconstriction in isolated human middle cerebral and basilar arteries. The vasoconstriction elicited by Aβ in these large human cerebral arteries appears to be completely antagonized by NS‐398, a selective cyclooxygenase‐2 inhibitor, or by SB202190, a specific p38 mitogen‐activated protein kinase inhibitor, suggesting that Aβ vasoactivity is mediated via the stimulation of a proinflammatory pathway. In addition, a similar proinflammatory response appears to be mediated by Aβ in isolated human brain microvessels, resulting in an increased production of prostaglandin E2 and F2α. Using a scanner laser Doppler imager, we show a progressive decline with aging in cortical perfusion level in transgenic APPsw mice (line 2576) compared with age‐matched control littermates. The relation between the acute proinflammatory and vasoactive properties of Aβ and the chronic progressive hypoperfusion seen in AD (and transgenic models thereof) is yet to be elucidated.
Astroglial Expression of the β‐Amyloid in Ischemia‐Reperfusion Brain Injury
Authors: PLUTA RYSZARD
Published: July 2009

Vascular damage and reactive gliosis are found colocalized with amyloid deposits in Alzheimer's disease brain, suggesting that the cerebrovasculature may be a clinically relevant site of Alzheimer's disease pathology and may contribute to the neurodegeneration process in Alzheimer's disease. In ischemic conditions, amyloid precursor protein and amyloid peptide are reported to be upregulated in neurons and in extracellular space. Expression and distribution of amyloid precursor protein and amyloid peptide in astroglial cells were examined immunohistochemically after 10‐min cardiac arrest. After reperfusion for 2, 7, and 14 days and 1, 6, 9, and 12 months, brains were immunostained. The indirect reactive astrocytes with fragments of the full‐length amyloid precursor protein were observed in brains until 7 days postischemia. Direct immunoreactivity only of amyloid peptide and the C‐terminal of amyloid precursor protein was also localized in the reactive astrocytes in ischemic brains at 6 months after ischemia. Ischemia temporarily induced amyloid peptide overexpression in reactive astrocytes, but this expression peaked at 7 days and 6 months. A glial appearance of amyloid peptide and C‐terminal of amyloid precursor protein staining occurred when extensive neuronal loss and the onset of brain atrophy were evident. The localization of the C‐terminal of amyloid precursor protein within ischemic astroglial cells underscores the likely importance of the C‐terminal of amyloid precursor protein in the pathogenesis of ischemia as in Alzheimer's disease.
Enhanced Aβ40 Deposition Was Associated with Increased Aβ42/43 in Cerebral Vasculature with Dutch‐Type Hereditary Cerebral Hemorrhage with Amyloidosis (HCHWA‐D)
Authors: OZAWA K. , TOMIYAMA T. , MAAT‐SCHIEMAN M. L. , ROOS R. A. , MORI H.
Published: July 2009

Abstract: Cerebrovascular deposition of the amyloid beta‐protein (Aβ) is a common pathologic event in patients with Alzheimer's disease (AD) and certain related disorders. Such an Aβ vascular deposition occurs primarily in the medial layer of the cerebral vessel wall in an assembled fibrillar state. These deposits are associated with several pathological responses, including degeneration of the smooth muscle cells in the cerebral vessel wall. Severe cases of cerebrovascular Aβ deposition are also accompanied by loss of vessel wall integrity and hemorrhagic stroke. Although the reasons for this pathological consequence are unclear, altered proteolytic mechanisms within the cerebral vessel wall may be involved. We analyzed cerebral Aβ deposition in brains with AD and Dutch‐type hereditary cerebral hemorrhage with amyloidosis (HCHWA‐D) on the basis of two amyloid species of Aβ40 and Aβ42/43 using specific monoclonal antibodies. Compared to Aβ deposition in senile plaques, the molecular composition of Aβ was distinguishable, indicating that the Aβ40 species is the main component for vascular amyloid. Furthermore, we found Aβ42/43 immunoreactivity was also much increased in amyloid angiopathy of all cases with HCHWA‐D. Taken together, amyloid angiopathy in HCHWA‐D may share an Aβ42‐driven deposition mechanism with plaque amyloid, resulting in enhanced Aβ40 deposition.
Neurocardiovascular Instability in Cognitive Impairment and Dementia
Authors: KENNY ROSE ANNE M. , KALARIA RAJ , BALLARD CLIVE
Published: July 2009

Abstract: Neurocardiovascular instability (NCVI, neurally mediated disorders causing hypotension with or without bradycardia) represents abnormal neural control of the cardiovascular system and presents as dizziness, syncope, or falls. The mechanisms underpinning NCVI are incompletely understood. The three most common disorders are carotid sinus syndrome (CSS), orthostatic hypotension (OH), and vasovagal syndrome (VVS): CSS, cardioinhibition > 3 s and/or vasodepressor response ≥ 50 mmHg drop in systolic pressure during carotid sinus stimulation; OH: fall in systolic blood pressure > 20 mmHg during standing; VVS: cardioinhibition > 3 s and/or vasodepressor response > 50 mmHg during prolonged head‐up tilting. In fallers with cognitive impairment or dementia, the prevalence of NCVI is 70%. Multifactorial interventions, including treatment of NCVI, significantly reduce falls and syncope. The predominant components of NCVI in fallers with cognitive impairment and dementia are CSS and OH. In Lewy body and Alzheimer's dementia, the prevalence of NCVI is up to 60%, again predominantly CSS and OH. The prevalence of cardioinhibitory carotid sinus hypersensitivity is particularly high in Lewy body dementia—41% compared with 12% in Alzheimer's disease and 3% in case controls. In addition, patients with Lewy body dementia have greater heart rate slowing (>2 s) and falls in systolic blood pressure (>20 mmHg) than those with Alzheimer's disease or controls during carotid sinus stimulation. The extent of deep white matter hyperintensities on MRI correlates with systolic fall during carotid sinus stimulation (R= 0.58; p < 0.005), suggesting a possible causal association between bradyarrhythmia‐induced hypotension and microvascular pathology. NCVI is common in patients with dementia and may be a reversible cause of falls and syncope. Repeated hypotensive episodes may exaggerate cognitive decline in these patients.
Decreased Cerebrospinal Fluid Levels of Neurosin (KLK6), an Aging‐Related Protease, as a Possible New Risk Factor for Alzheimer's Disease
Authors: MITSUI SHINICHI , OKUI AKIRA , UEMURA HIDETOSHI , MIZUNO TOSHIKI , YAMADA TATSUO , YAMAMURA YOSHIO , YAMAGUCHI NOZOMI
Published: July 2009

Abstract: Neurosin is a kallikrein‐like serine protease expressed preferentially in the human brain. It is localized in senile plaques and neurofibrillary tangles in the brains of individuals with Alzheimer's disease (AD) and in Lewy bodies in patients with Parkinson's disease. Neurosin is present in the cerebrospinal fluid (CSF) as a proenzyme and does not show any enzymatic activity. We have developed a sandwich ELISA system using monoclonal and polyclonal antibodies against human neurosin and have measured neurosin levels in the CSF from AD and non‐CNS disease patients. Both male and female patients with peripheral neuropathy showed statistically positive correlations between CSF neurosin concentrations and age (males, n= 52, r= 0.482, p < 0.005; females, n= 43, r= 0.365, p < 0.005). In contrast, such positive correlation was not observed in the CSF from patients with AD. Further, some such patients showed extremely low levels of CSF neurosin. Our results suggest that neurosin is an aging‐related protease and that a decreased CSF concentration of neurosin may be a risk factor for developing AD.
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) and CADASIL‐Like Disorders in Japan
Authors: UCHINO M. , HIRANO T. , UYAMA E. , HASHIMOTO Y.
Published: July 2009

Abstract: We reviewed 12 patients from 11 Japanese families diagnosed as having CADASIL from 1998 to 2001. The age of onset of focal neurologic deficits ranged from 38 to 71 years (mean: 50.4 ± 9.8 years). Japanese CADASIL patients rarely had migraine and frequently presented with symptoms of dementia at diagnosis. Notch3 mutations were concentrated in exons 3, 4, and 5. Cysteine was replaced by another amino acid or vice versa in the majority of Japanese CADASIL patients. However, in 2 families, the mutations were not related to cysteine. In the prospective study, 2030 patients with stroke were hospitalized in 6 hospitals with stroke units in the Kumamoto district from 1999 to 2001. Among them, 14 patients fulfilled the criteria of being less than 60 years of age, showing lacunar strokes and/or TIA, presence of a family history, and no risk factors of stroke. One of these 14 patients was diagnosed as having CADASIL by DNA analysis. However, if hyperlipidemia was excluded from the list, 16 patients fulfilled the criteria and 2 patients were diagnosed as having CADASIL by DNA analysis. It was suspected that the incidence of CADASIL is not so rare in Japan. There were some families with CADASIL‐like features, but without Notch3 mutations or GOM, suggesting the need for genetic analysis in the future.
Vascular Pathology in Alzheimer's Disease
Authors: MIYAKAWA TAIHEI
Published: July 2009

Abstract: This report briefly describes the morphological examination in several types of senile plaques made by using serial sections for both light and electron microscopy in order to observe the relationship between senile plaques and cerebral microvessels.
Treatment of Alzheimer's Disease by Transposition of the Omentum
Authors: GOLDSMITH HARRY S.
Published: July 2009

Abstract: There is increasing evidence that cerebral hypoperfusion plays a key role in the development of Alzheimer's disease (AD). As one ages, cerebral blood flow (CBF) decreases as a direct reflection of a normal aging process. Coupled with this expected drop in CBF are a host of other factors, such as hypertension, stress, smoking, diabetes, cholesterol buildup, etc., which further decrease blood flow to the brain. Maintaining a critical level of CBF is essential if adequate amounts of oxygen and glucose are to be presented to neurons to sustain their cellular energy production (ATP). If CBF drops below a critical flow level, insufficient ATP will be produced and, if this situation is not corrected, neurons will deteriorate and eventually die. When a critical mass of neurons die in areas of the brain involved with cognition and memory, AD will result. Omentum transposition to the brain is a surgical procedure by which a large volume of blood and other biological agents can be delivered to the brain over an indefinite period of time. The omentum gives metabolic support to deteriorating neurons and its presence on the brain has resulted in the reversal of AD symptoms. Additionally, omentum transposition to the brain can markedly reduce senile plaque accumulation, but has no apparent effect on reducing neurofibrillary tangles. Omental transposition may play an important role in the future treatment of AD, especially in early and moderate cases.
Lymphangiogenesis New Mechanisms
Authors: CHANG LYNN , KAIPAINEN ARJA , FOLKMAN JUDAH
Published: July 2009

Abstract: A mouse model has been developed to study lymphangiogenesis dissociated from angiogenesis. bFGF implanted in a mouse cornea at a concentration below the threshold to induce angiogenesis potently induces lymphangiogenesis. This model has permitted a study of cellular and molecular mechanisms of lymphangiogenesis.
Content‐Based Ultrasound Image Retrieval Using a Coarse to Fine Approach
Authors: KWAK DONG‐MIN , KIM BUM‐SOO , YOON OCK‐KYUNG , PARK CHUL‐HYUN , WON JONG‐UN , PARK KIL‐HOUM
Published: July 2009

Abstract: One of the current issues for picture archiving and communication systems (PACS) is extending retrieval technologies to deal with multimedia information. This is particularly important for medical applications that assist in diagnostic processes and pathology studies. Accordingly, this paper presents a new approach to content‐based image retrieval (CBIR) for a clinical ultrasound image database (DB). The proposed algorithm consists of two stages so as to maximize the retrieval efficiency. In the first stage, a coarse retrieval is performed using the statistical characteristics of the wavelet coefficients that narrow the search by eliminating up to 70% of the total DB images. In the second stage, a fine retrieval is carried out using the Legendre moment of the global histogram pdf on the reduced image set preretrieved by the coarse retrieval. When tested on an abdominal ultrasound image DB and compared with various other methods, the proposed algorithm gave promising results for applying CBIR to clinical ultrasound images.
Image Study Summarization of MR Brain Images by Automated Localization of Relevant Structures
Authors: SINHA USHA , KANGARLOO HOOSHANG
Published: July 2009

Abstract: The paper discusses a methodology to objectify the patient presenting condition by automated selection of relevant images from a serial MR study. Structured data entry is used to capture the patient's chief complaint, pertinent history, signs, and symptoms. Expert created rules use this data to arrive at a differential and to identify the affected brain region/structure. Another expert created knowledge base then maps this information to the relevant image type, including image sequence specifics and orientation. A DICOM study reader identifies the relevant imaging sequences from the MR study. The structure localization method involves a search based on principal component analysis. A training set of subimages containing the structure of interest is used to generate a basis set of prototype images called eigenimages. The structure is located in an image by searching the image for a subregion that best matches the basis set. The structure localization was used to locate the lateral ventricles and orbits in nine images that were not part of the training set. The automated localizations were compared to expert localizations and the center of the regions located by the two techniques agreed to within ± 1.7 mm (average for the nine localizations each of two structures).
Advances in Biomedical Informatics for the Management of Cancer
Authors: HAQUE SYED , MITAL DINESH , SRINIVASAN SHANKAR
Published: July 2009

Abstract: Increased access to health care, and advances in education and technology have resulted in a larger proportion of the population having longer life expectancy. The strong correlation between age and cancer has resulted in a major healthcare problem for this century, and until recently cancer has defied any long‐lasting cure. However, progress, especially in the field of biomedical informatics, promises a successful prediction and possibly a permanent cure for cancer within the next two decades. Biomedical informatics—with its roots in computer science, biomedical engineering, biostatistics, and mathematics—helps to bring the patient closer to the physician, facilitates access to specialist information and knowledge bases across the world, and makes it possible to identify genetic expression profiles for malignant or cancerous cells. This paper reviews the new research findings in biomedical informatics, working toward the ultimate goal of successfully predicting cancer, solving complex problems in prevention and treatment of cancer, and perhaps completely curing the scourge of cancer.