bluuebunny/crossref_metadata_2025 huggingface dataset:
Atrophic gastritis in young children and adolescents
Authors: Ricuarte O , Gutierrez O , Cardona H , Kim J G , Graham D Y , El-Zimaity H M T
Published: October 2005

Background:Helicobacter pyloriassociated gastric cancer arises via a multistage process, with atrophic gastritis being the precursor lesion.Helicobacter pyloriis typically acquired in childhood, yet little is known of the prevalence of atrophic gastritis in childhood.

Aim:To study atrophic gastritis among children from countries with high gastric cancer incidence.

Methods:Sections from topographically mapped gastric biopsy specimens from children undergoing clinically indicated endoscopy in Korea and Colombia were evaluated using visual analogue scales. Atrophy was defined as loss of normal glandular components, including replacement with fibrosis, intestinal metaplasia (IM), and/or pseudopyloric metaplasia of the corpus (identified by the presence of pepsinogen I in mucosa that was topographically corpus but phenotypically antrum).

Results:One hundred and seventy three children, 58 from Korea (median age, 14 years) and 115 from Colombia (median age, 13 years), were studied.Helicobacter pyloriwas present in 85% of Colombian children versus 17% of Korean children (p<0.01). Atrophic mucosa near the antrum–corpus border was present in 16% of children, primarily as pseudopyloric metaplasia (31%, IM; 63%, pseudopyloric metaplasia; 6%, both). The median age of children with corpus atrophy was 15 (range, 7–17) years.

Conclusion:Gastric atrophy occurs inH pyloriinfected children living in countries with high gastric cancer incidence. Identification and characterisation of the natural history ofH pylorigastritis requires targeted biopsies to include the lesser and greater curve of the corpus, starting just proximal to the anatomical antrum–corpus junction, in addition to biopsies targeting the antrum and cardia.
Rat bite fever caused byStreptobacillus moniliformisin a child: human infection and rat carriage diagnosed by PCR
Authors: Andre J-M , Freydiere A M , Benito Y , Rousson A , Lansiaux S , Kodjo A , Mazzocchi C , Berthier J-C , Vandenesch F , Floret D
Published: October 2005

A child owning pet rats developed an eruptive fever with blisters, polyarthritis, and spectacular desquamation of the hands.Streptobacillus moniliformiswas identified after culture of the child’s blister fluid and was detected in rat samples by molecular methods. Such detection in the pet of a human victim of rat bite fever has not been reported previously.
Aberrant expression of ΔNp73 in benign and malignant tumours of the prostate: correlation with Gleason score
Authors: Guan M , Chen Y
Published: October 2005

Background:The p73 gene is a p53 homologue that induces apoptosis and inhibits cell proliferation. N-terminal truncated isoforms of p73 (ΔNp73) act as dominant-negative inhibitors of wild-type p53 and TAp73 and result in tumour growth in nude mice.

Aims:To detect ΔNp73 expression in 24 benign prostatic hyperplasia samples, 33 prostate carcinomas, and five normal samples and to evaluate the relation between ΔNp73, TAp73 concentrations, and the clinicopathological characteristics of patients with prostate cancer.

Methods:TAp73 was determined by real time polymerase chain reaction (PCR); ΔNp73 and ΔN’p73 were assessed using reverse transcription PCR. western blotting was used to analyse protein expression. p53 mutation was determined by immunohistochemistry.

Results:A significant increase of ΔNp73 was seen in 20 of 33 carcinomas and 17 of 24 benign prostate hyperplasia tissues, but in none of the normal samples. None of the specimens expressed ΔN’p73. No significant relation was found between TAp73 expression and clinical parameters. The incidence of positive expression of ΔNp73 correlated with the Gleason score in prostate carcinomas. Cancer samples with wild-type p53 had significantly higher expression of ΔNp73 than p53 mutant cancers.

Conclusion:These data suggest a potential role for ΔNp73 in prostate cancer progression.
Serous adenocarcinoma of the sigmoid mesentery arising in cystic endosalpingiosis
Authors: McCoubrey A , Houghton O , McCallion K , McCluggage W G
Published: October 2005

This case report describes a Mullerian serous adenocarcinoma arising within a multoloculated cyst lined by ciliated serous-type epithelium located in the sigmoid mesentery. Twenty years previously the patient underwent a hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. The ovaries contained bilateral serous cystadenofibromas, and multiple cysts lined by ciliated serous-type epithelium were present in the omentum. The resection specimen 20 years later contained a 14 cm multiloculated cyst located in the sigmoid mesentery. This was lined largely by benign ciliated serous-type epithelium but a focus of well differentiated serous adenocarcinoma projected into the lumen. Two further peritoneal cysts were present, both of which were lined by ciliated serous-type epithelium. There was a coincidental renal cell carcinoma. This is a unique case of multiple omental, peritoneal, and retroperitoneal cysts (classified as cystic endosalpingiosis), one of which developed a focus of serous adenocarcinoma. Although rarely serous adenocarcinomas, similar to those occurring within the ovary, arise in the retroperitoneum, this is the first reported occurrence in association with a pre-existing benign lesion.
A MODEL OF BOSE–EINSTEIN CONDENSATION WITH ITINERANT AND LOCALIZED STATES
Authors: HAN FUXIANG , REN ZHIRU , GAO YUN'E
Published: October 2005

We propose a model that includes itinerant and localized states to study Bose–Einstein condensation of ultracold atoms in optical lattices (Bose–Anderson model). It is found that the original itinerant and localized states intermix to give rise to a new energy band structure with two quasiparticle energy bands. We have computed the critical temperature Tc of the Bose–Einstein condensation of the quasiparticles in the Bose–Anderson model using our newly developed numerical algorithm and found that Tc increases as na3 (the number density times the lattice constant cubed) increases according to the power law Tc≈18.93(na3)0.59 nK for na3<0.125 and according to the linear relation Tc≈8.75+10.53na3 nK for 1.25<na3<12.5 for the given model parameters. With the self-consistent equations for the condensation fractions obtained within the Bogoliubov mean-field approximation, the effects of the on-site repulsion U on the quasiparticle condensation are investigated. We have found that, for values up to several times the zeroth-order critical temperature, U enhances the zeroth-order condensation fraction at intermediate temperatures and effectively raises the critical temperature, while it slightly suppresses the zeroth-order condensation fraction at very low temperatures.
IMPLOSION DYNAMICS OF HIGH-DENSITY FIBER PLASMA DRIVEN BY IMPLODING MULTICASCADE LINER
Authors: DEEBA FARAH , AHMED KAMALUDDIN , HASEEB MAHNAZ QADAR , MIRZA ARSHAD M.
Published: October 2005

The dynamics of a high density D-T fiber plasma driven by a multi cascade system (N multiple shells of finite thicknesses) has been investigated with a view to suppress Rayleigh–Taylor (R–T) instability. Our numerical results show that the plasma parameters of the D-T fiber sensitively depends upon the shell mass ratios and thicknesses. Large values of puff-thickness and mass-ratios provide stabilization against the R–T instability in the final stage of compression but adversely affect fusion conditions. Our analysis, however, suggests that optimum values of the puff-thicknesses and mass ratios are needed to achieve fusion parameters in a multi cascade liner staged Z-pinch devices. The relevance of our present investigation to ultra high magnetic fluxes, X-ray lasers as well as controlled thermonuclear fusion is also pointed out.
STUDY OF EPITAXIAL GROWTH OF DIAMOND FILM ON HETERO-MATERIAL SUBSTRATE
Authors: LIAO YUAN , YU QINGXUAN , WANG GUANZHONG , FANG RONGCHUAN
Published: October 2005

We study the epitaxial growth mechanism of diamond films using various hetero-materials as substrates in a hot-filament chemical vapor deposition (HFCVD) chamber. The same parameters were maintained in the nucleation and growth processes of diamond films on these substrates. The experimental results showed that the dominant orientation of diamond crystals has a relation with that of substrates identified by X-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques. The preference of diamond films on non-diamond substrates is explained as heteroepitaxial growth. We think that the initial nucleation process is the key to the heteroepitaxial growth of diamond film.
DEPOSITION OF CHROMIUM-CARBON FILMS BY MAGNETRON SPUTTERING OF CHROMIUM AND CARBON TARGETS
Authors: HOU Q. R. , ZHANG H. Y. , CHEN Y. B.
Published: October 2005

Chromium-carbon films have been deposited on silicon substrates by magnetron sputtering of chromium and carbon targets in pure argon atmosphere. The composition of the films was examined by Auger electron spectroscopy. Oxygen, nitrogen, and iron were the major impurities incorporated in the films. The mechanical and electrical properties of the films were investigated as a function of negative bias voltage applied to substrates. The hardness and elastic modulus were measured by a nano-indenter and the values are around 17.0±0.9 GPa and 245±11 GPa , respectively. The hardness and elastic modulus of the films increased while the electrical resistivity decreased when the substrate bias voltage was applied. The lowest resistivity (~ 267 μ ohm-cm ) was obtained at the substrate bias voltage of 50 V. The temperature dependence of resistivity of the films was measured in air from room temperature to 673 K. The time dependence of resistivity of the films was also measured in air at 673 K. It was found that the resistivity changed little with temperature or time.
CLASSICAL PHASE FLUCTUATIONS IN d-WAVE SUPERCONDUCTORS
Authors: SAMOKHIN K. V. , MITROVIĆ B.
Published: October 2005

We study the effects of low-energy nodal quasiparticles on the classical phase fluctuations in a two-dimensional d-wave superconductor. The singularities of the phase-only action at T→0 are removed in the presence of disorder, which justifies using an extended classical XY-model to describe phase fluctuations at low temperatures.
A NONLINEAR UNIFIED STATE-SPACE MODEL FOR SHIP MANEUVERING AND CONTROL IN A SEAWAY
Authors: FOSSEN THOR I.
Published: October 2005

This article presents a unified state-space model for ship maneuvering, station-keeping, and control in a seaway. The frequency-dependent potential and viscous damping terms, which in classic theory results in a convolution integral not suited for real-time simulation, is compactly represented by using a state-space formulation. The separation of the vessel model into a low-frequency model (represented by zero-frequency added mass and damping) and a wave-frequency model (represented by motion transfer functions or RAOs), which is commonly used for simulation, is hence made superfluous.
MATHEMATICAL METHODS AND TOOLS OF KINETIC THEORY TOWARDS MODELLING COMPLEX BIOLOGICAL SYSTEMS
Authors: BELLOUQUID ABDELGHANI , DELITALA MARCELLO
Published: October 2005

This paper develops a variety of mathematical tools to model the dynamics of large systems of interacting cells. Interactions are ruled not only by laws of classical mechanics, but also by some biological functions. The mathematical approach is the one of kinetic theory and non-equilibrium statistical mechanics. The paper deals both with the derivation of evolution equations and with the design of specific models consistent with the above-mentioned mathematical framework. Various hints for research perspectives are proposed in the last part of the paper.
MICRO AND MESO SCALES OF DESCRIPTION CORRESPONDING TO A MODEL OF TISSUE INVASION BY SOLID TUMOURS
Authors: LACHOWICZ MIROSŁAW
Published: October 2005

In this paper two new mathematical models are proposed that correspond to a macroscopic model of tissue invasion of solid tumours, in terms of a system of reaction-diffusion-chemotaxis equations. The first model is defined at the micro-scale level of a large number of interacting individual entities, and is in terms of a linear (Markov) equation. The second model refers to the meso-scale level of description of test-entities and is given in terms of a bilinear Boltzmann-type equation. Mathematical relationships among these three possible descriptions are formulated. Explicit error estimates are given.
MATHEMATICAL MODELLING OF CANCER CELL INVASION OF TISSUE: THE ROLE OF THE UROKINASE PLASMINOGEN ACTIVATION SYSTEM
Authors: CHAPLAIN M. A. J. , LOLAS G.
Published: October 2005

The growth of solid tumours proceeds through two distinct phases: the avascular and the vascular phase. It is during the latter stage that the insidious process of cancer invasion of peritumoral tissue can and does take place. Vascular tumours grow rapidly allowing the cancer cells to establish a new colony in distant organs, a process that is known as metastasis. The progression from a single, primary tumour to multiple tumours in distant sites throughout the body is known as the metastatic cascade. This is a multistep process that first involves the over-expression by the cancer cells of proteolytic enzyme activity, such as the urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs). uPA itself initiates the activation of an enzymatic cascade that primarily involves the activation of plasminogen and subsequently its matrix degrading protein plasmin. Degradation of the matrix then enables the cancer cells to migrate through the tissue and subsequently to spread to secondary sites in the body.

In this paper we consider a mathematical model of cancer cell invasion of tissue (extracellular matrix) which focuses on the role of the plasminogen activation system. The model consists of a system of reaction-diffusion-taxis partial differential equations describing the interactions between cancer cells, urokinase plasminogen activator (uPA), uPA inhibitors, plasmin and the host tissue. The focus of the modelling is on the spatio-temporal dynamics of the uPA system and how this influences the migratory properties of the cancer cells through random motility, chemotaxis and haptotaxis. The results obtained from numerical computations carried out on the model equations produce rich, dynamic heterogeneous spatio-temporal solutions and demonstrate the ability of rather simple models to produce complicated dynamics, all of which are associated with tumour heterogeneity and cancer cell progression and invasion.
A MATHEMATICAL MODEL FOR TUMOR CORDS INCORPORATING THE FLOW OF INTERSTITIAL FLUID
Authors: BERTUZZI ALESSANDRO , FASANO ANTONIO , GANDOLFI ALBERTO
Published: October 2005

This work extends a previous model that described the evolution of a tumor cord (a cylindrical arrangement of tumor cells, generally surrounded by necrosis, growing around a blood vessel of the tumor) under the activity of cell killing agents. In the present model we include the most relevant aspects of the dynamics of extracellular fluid, by computing the longitudinal average of the radial fluid velocity and of the pressure field. We still assume that the volume fraction occupied by the cells always keeps the same constant value everywhere in the cord. The necrotic region is treated as a "fluid reservoir". To improve the modelling of therapeutic treatment, we have subdivided the viable cell population into a proliferating and a quiescent subpopulation. The transitions between the two states are both permitted, and are regulated by rates depending on the local oxygen concentration. For simplicity, the rates of death induced by treatment are assumed to be known functions of the radial distance and time. Existence and uniqueness of the stationary state in the absence of treatment has been shown, as well as the existence and uniqueness of the evolution that arises following a cell killing treatment.
MATHEMATICAL MODELLING OF GLIOBLASTOMA TUMOUR DEVELOPMENT: A REVIEW
Authors: HATZIKIROU HARALAMPOS , DEUTSCH ANDREAS , SCHALLER CARLO , SIMON MATTHIAS , SWANSON KRISTIN
Published: October 2005

During the past several years mathematical models have been applied to various aspects of cancer dynamics, in particular avascular and vascular tumour growth, invasion, angiogenesis, and metastasis. This paper focuses on the most common and malignant brain tumour, glioblastoma, and surveys the growing number of studies dealing with mathematical modelling of this tumour. We attempt to classify these studies by their biomedical relevance and critically analyse their results. The aim of this review is to provide a meaningful reference, to both biomedical and mathematical researchers, of the current state of the art of glioma tumour modelling. The discussion attempts to identify current open problems as well as new research perspectives in the mathematical modelling of glioblastoma growth.
EVALUATION OF CERVICAL RANGE OF MOTION IN A CERVICAL RADICULOPATHY PATIENT GROUP AND A MATCHED CONTROL GROUP USING THE SPIN-T GONIOMETER
Authors: Agarwal Shabnam , Allison Garry T , Singer Kevin P
Published: October 2005

Forty- six cervical radiculopathy patients, age- and gender-matched with 43 controls, recruited in this study were measured for end-range flexion, extension, lateral rotation right and left using the Spin-T goniometer. Within group differences were calculated using a paired t-test and differences between groups were compared using an independent sample t-test at p < 0.05. The results showed that the mean cervical spine ROM in the cervical radiculopathy group was reduced compared to matched controls for flexion (t = 2.26, p = 0.02), extension (t = 2.30, p = 0.02) and full cycle rotation (sum of left and right rotation) (t = 2.01, p = 0.04). Differences calculated within normal controls and the patients for paired rotation movements were not significant. Cervical ROM comparisons between a cervical radiculopathy patient cohort and a normal control group indicate a trend toward limitation of ROM compared to normal controls although it does not seem to be a systematic feature of the pain population as tested in this study. The reduction was not unilaterally patterned and did not show any difference in individual movements of the cervical spine when compared to any one painful side.
MAGNETIC RESONANCE RELAXATION-TIME STUDIES OF FRACTURE REPAIR IN CHICKS: A POTENTIAL METHOD FOR EVALUATION OF FRACTURE HEALING
Authors: Nusem I. , Edelstein S. , Otremski I.
Published: October 2005

Purpose: To investigate whether magnetic resonance relaxation-time measurements have a role in monitoring fracture healing.

Methods: Magnetic resonance relaxation-time measurements were used to assess callus formation in chicks' tibiae and were correlated to the histopathologic and biomechanical changes that occur throughout the process of fracture repair.

Results: The effective transverse relaxation time (T2) values recorded during fracture healing process were significantly longer (p = 0.0151) at day 14 (65.5575 ms.), compared with those recorded at days 3 (52.68 ms.) and 7 (55.4313 ms.). The T2 values distributions (a) at day 14 (0.2304) were significantly lower (p = 0.0313) compared with those recorded at days 7 (0.2721) and 10 (0.2742). Using a semiquantitative histologic evaluation, a significant increase in the amount of endosteal new bone (p = 0.048), and periosteal new bone (p = 0.008), associated with a significant decrease in the amount of old bone (p = 0.007) and cartilaginous tissue (p = 0.001) was observed. Analysis of the torque-angle curves demonstrated a low torque and a large angular deformation associated with low stiffness at 3–7 days post-fracture, and a high torque and a small angular deformation associated with high stiffness at 10–14 days post-fracture.

Interpretation: Magnetic resonance relaxation-time follows the histopathologic and biomechanical changes occurring during the process of fracture repair and it may have a role as a potential method for objective estimation of fracture repair.
EQUILIBRIUM CONDITIONS OF FORWARD EXCHANGE MARKET EXPRESSED IN A SIMPLE GEOMETRIC STRUCTURE
Authors: CHEN JIANGUO , BLENMAN LLOYD P.
Published: October 2005

The paper focuses on the market equilibrium conditions in forward exchange quotes. By careful analysis of the market arbitrage conditions, market supply and demand, we construct the equilibrium ranges for bid and ask forward quotes separately. We present our analysis in a bid-ask cost structure setting, and directly tie the equilibrium and arbitrage conditions to specific trading strategies. We conclude that in equilibrium there will be no chance for one-way-arbitrage in foreign exchange and securities markets, provided that non-reversed traders are active and set the arbitrage boundaries. The framework we develop in the paper is convenient for academic study and practical use in currency and security markets.
Laterite geochemistry applied to diamond exploration in the Yilgarn Craton, Western Australia
Authors: Cornelius Matthias , Singh Balbir , Meyer Stephan , Smith Raymond E. , Cornelius Amanda J.
Published: October 2005

This paper describes an exploration programme based on regional laterite sampling (1 to 9 km spacing) aimed at locating geochemical anomalies of kimberlite pipes. Orientation studies at the Aries pipe, Western Australia, and several pipes in the Coromandel area in the state of Minas Gerais, Brazil, demonstrated that lateritic residuum on kimberlite reflects the characteristic geochemical signature of the bedrock. Data interpretation by identifying and ranking geochemical anomalies of alkaline ultramafic rocks in regional multi-element datasets was done using univariate and multivariate statistics. These techniques can also test the datasets for other mineral occurrences, such as rare metals. Although this study did not locate a kimberlite pipe, regional geochemical sampling identified an area (46 Gate Road anomaly near Lake Brown) in the northern Merredin region where lateritic ferruginous materials appear to have formed on mafic–ultramafic alkaline bedrock, possibly an ultramafic lamprophyre that had not previously been recognized. Other regional geochemical features identified by this study, and yet to be followed up, include a Ta–Sn–Nb anomaly SE of Meekatharra, a Ni–Cu–Zn–Co anomaly in an area NE of Lake Barlee, an As–Cr–Sb–(Ni–Co–Mn–Mg) anomaly east of the Youanmi greenstone belt, and a Mg–Cr–Co anomaly in the very southern part of the survey area.

The deeply weathered terrains of the Yilgarn Craton and adjacent Proterozoic belts in Western Australia present difficult environments for diamond exploration and to date no economic diamond pipes have been found in the Yilgarn Craton. With the exception of diamond and chromite, indicator minerals are destroyed through intense weathering, with very short dispersion trails of any remaining minerals in a dominantly low-relief landscape. The use of aeromagnetic data is limited by deep weathering causing noisy magnetic backgrounds in areas with preserved lateritic residuum due to contained maghemite. Additional problems arise from variably magnetic granites and gneisses, and greenstone remnants within them. Electromagnetic techniques are often adversely affected by highly conductive overburden.

Laterite geochemistry applied within a regolith–landform framework has the potential to be a complementary technique for diamond exploration in deeply weathered terrain. It can be used to test geophysical targets in areas with a preserved lateritic mantle and to explore for pipes that may have obscure geophysical signatures. Orientation studies, using ferruginous gravels and duricrust formed on alkaline ultramafic and ultramafic rocks, show characteristic geochemical signatures with a halo about three times larger than the pipe itself due to mechanical and hydromorphic dispersion within the regolith.
Geochemical mapping at the Geological Survey of Sweden
Authors: Lax Kaj , Selinus Olle
Published: October 2005

Geochemical mapping has been carried out for several decades at the Geological Survey of Sweden (SGU). Two kinds of sampling media dominate: glacial till (soil geochemical programme) and aquatic vegetation (biogeochemical mapping). Data from these mapping programmes have been used for various applications such as discoveries of contaminated land and research in environmental, medical and mineral exploration.

The main goal of the geochemical mapping programmes has been to produce consistent and high quality data. Therefore, both programmes have been subject to various changes to increase their usefulness for decision-makers and planners. The number of parameters determined has increased, partial leach analysis has migrated from a combination of AAS/ICP-AES techniques to ICP-MS, urban geochemistry projects have been incorporated, and additional terrestrial sediments have been added to the regional soil geochemical survey. An increasing number of new applications have also been implemented for emerging societal needs.

This paper gives an overview of the mapping programme and examples of products for use in society as well as strategies for the future.
Copper geochemistry in salt from evaporite soils, Coastal Range of the Atacama Desert, northern Chile: an exploration tool for blind Cu deposits
Authors: Palacios Carlos , Guerra Nelson , Townley Brian , Lahsen Alfredo , Parada Miguel
Published: October 2005

The evaporite soil (1.5 to 15 m thick) in the Coastal Range of northern Chile is a serious obstacle to mineral exploration. We conducted a Cu geochemical study in salt beds (mainly gypsum and anhydrite) from this soil. The sampling was distributed over mineralized and barren rocks, in salts of evaporitic soils from hills, slopes, gullies, plains and alluvium-filled valleys. The samples of salt from hills and slopes reflect very well the presence of blind ore deposits, and the magnitude of the Cu anomalies (<200 to >1000 ppm Cu) is independent of the depth at which the mineralization is located. Similar geochemical response has been found in salt from evaporitic soils that cover gullies, plains and alluvium-filled valleys. However, in the last case the magnitude of the Cu anomalies (<20 to >200 ppm Cu) depends on the thickness of the gravels and the depth of leached bedrock that covers the blind deposits. Although the Cu anomalies are spiky, their contrast with the background Cu population is remarkable. Sampling of salt from evaporitic soils appears to be a valuable tool for exploration of buried Cu deposits in the exceedingly arid Coastal Range of the Atacama Desert.
HETEROGENEOUS CHEMISTRY OF CARBON AEROSOLS
Authors: Nienow Amanda M. , Roberts Jeffrey T.
Published: October 2005

▪ Abstract  Atmospheric carbon particles originate from natural sources and from human activity. The processes that lead to their formation are varied and include fossil fuel combustion, biomass burning, and mechanical stress and wear of carbonaceous materials. In this review, we examine recent work on the structure and composition of carbon aerosol particles, and we describe how they react with the atmospherically abundant gases ozone, oxygen, sulfur dioxide, nitric acid, and nitrogen oxides. The study of carbon particles in the laboratory has shown that chemical reactivity depends strongly on the type of carbon used and on experimental conditions such as temperature and humidity. The variability in the results demonstrates the difficulty in extrapolating laboratory results to atmospheric conditions and in explaining the role of carbon particles in processes such as global warming and environmental chemical cycling.
Innate immune responses of human tracheal epithelium to Pseudomonas aeruginosa flagellin, TNF-α, and IL-1β
Authors: Tseng Jill , Do Jiun , Widdicombe Jonathan H. , Machen Terry E.
Published: October 2005

We measured innate immune responses by primary human tracheal epithelial (HTE) cells grown as confluent, pseudostratified layers during exposure to inflammatory activators on apical vs. basolateral surfaces. Apical Pseudomonas aeruginosa strain PAK (but not flagellin mutant PAK·fliC), flagellin, and flagellin + PAK·fliC activated NF-κB and IL-8 expression and secretion. In contrast, HTE cells were insensitive to LPS compared to flagellin. Flagellin activated NF-κB in columnar but not basal cells. IL-1β + TNF-α elicited responses similar to those of flagellin. Basolateral flagellin or IL-1β + TNF-α caused 1.5- to 4-fold larger responses, consistent with the fact that NF-κB activation occurred in both columnar and basal cells. MyD88 (toll receptor-associated adapter), IL-1 receptor (IL1R)1, and TNF-α receptor (TNFR)1 were expressed in columnar and basal cells. ZO-1 was localized to tight junctions of columnar cells but not to basal cells. We infer the following. 1) Flagellin is necessary and sufficient to trigger inflammatory responses in columnar cells during accumulation of P. aeruginosa in the airway surface liquid (ASL); columnar cells express toll-like receptor 5 and MyD88, often associated with flagellin-activated cell signaling. 2) IL-1β + TNF-α in the ASL also activate columnar cells, and these cells also express IL1R1 and TNFR1. 3) Apical flagellin, IL-1β, and TNF-α do not activate basal cells because tight junctions between columnar cells prevent access from the apical surface to the basal cells. 4) Exposure of basolateral surfaces to inflammatory activators elicits larger responses because both columnar and basal cells are activated, likely because both cell types express receptors for flagellin, IL-1β, and TNF-α.
Multiple eicosanoid-activated nonselective cation channels regulate B-lymphocyte adhesion to integrin ligands
Authors: Liu Xiaohong , Zhu Peimin , Freedman Bruce D.
Published: October 2005

Arachidonic acid (AA) is a substrate for a variety of proinflammatory mediators, which are generated by cyclooxygenases (COXs), lipoxygenases (LOXs), and cytochrome P-450 (CYP450) enzymes. COX (e.g., PGs and prostacyclins) and LOX (e.g., leukotrienes) products have well-established proinflammatory roles; however, little is known about the functions of CYP450 products in leukocytes. We previously found that mechanical strain generated by subjecting lymphocytes to hypotonic challenge triggered AA production and that two CYP450 products of AA, 5,6-epoxyeicosatrienoic acid (5,6-EET) and 20-hydroxyeicosatetraenoic acid (20-HETE), as well as a product of LOX, 5-( S)-hydroperoxyeicosatetrenoic acid (5-HPETE), induced Ca2+ entry into primary B cells. The main goal of the present studies, therefore, was to define the biophysically properties of eicosanoid-activated channels responsible for Ca2+ entry and the physiological consequences of activating these channels, including their role in mechanical signaling. We found that 5,6-EET, 20-HETE, and 5-HPETE each activated distinct Ca2+-permeant nonselective cation channels (NSCCs) in primary B cells. These NSCCs each regulate plasma membrane potential and B-cell adhesion to integrin ligands ICAM-1 and VCAM-1. Thus our data demonstrate that proinflammatory mediators produced in response to osmotic and/or physical stress play a direct role in regulating the B-cell membrane potential and their adhesion to specific ECM proteins. These results not only have important implications for understanding normal mechanisms of B-cell activation, differentiation, and trafficking but also point to novel targets for modulating the pathogenesis of B-cell-mediated inflammatory diseases.
ERK/MAPK regulates the Kv4.2 potassium channel by direct phosphorylation of the pore-forming subunit
Authors: Schrader Laura A. , Birnbaum Shari G. , Nadin Brian M. , Ren Yajun , Bui Duy , Anderson Anne E. , Sweatt J. David
Published: October 2005

Kv4.2 is the primary pore-forming subunit encoding A-type currents in many neurons throughout the nervous system, and it also contributes to the transient outward currents of cardiac myocytes. A-type currents in the dendrites of hippocampal CA1 pyramidal neurons are regulated by activation of ERK/MAPK, and Kv4.2 is the likely pore-forming subunit of that current. We showed previously that Kv4.2 is directly phosphorylated at three sites by ERK/MAPK (T602, T607, and S616). In this study we determined whether direct phosphorylation of Kv4.2 by ERK/MAPK is responsible for the regulation of the A-type current observed in neurons. We made site-directed mutants, changing the phosphosite serine (S) or threonine (T) to aspartate (D) to mimic phosphorylation. We found that the T607D mutation mimicked the electrophysiological changes elicited by ERK/MAPK activation in neurons: a rightward shift of the activation curve and an overall reduction in current compared with wild type (WT). Surprisingly, the S616D mutation caused the opposite effect, a leftward shift in the activation voltage. K+ channel-interacting protein (KChIP)3 ancillary subunit coexpression with Kv4.2 was necessary for the T607D effect, as the T607D mutant when expressed in the absence of KChIP3 was not different from WT Kv4.2. These data suggest that direct phosphorylation of Kv4.2 at T607 is involved in the dynamic regulation of the channel function by ERK/MAPK and an interaction of the primary subunit with KChIP is also necessary for this effect. Overall these studies provide new insights into the structure-function relationships for MAPK regulation of membrane ion channels.
Nongenomic regulation by aldosterone of the epithelial NHE3 Na+/H+exchanger
Authors: Good David W. , George Thampi , Watts Bruns A.
Published: October 2005

The relevance of nongenomic pathways to regulation of epithelial function by aldosterone is poorly understood. Recently, we demonstrated that aldosterone inhibits transepithelial HCO3−absorption in the renal medullary thick ascending limb (MTAL) through a nongenomic pathway. Here, we examined the transport mechanism(s) responsible for this regulation, focusing on Na+/H+exchangers (NHE). In the MTAL, apical NHE3 mediates H+secretion necessary for HCO3−absorption; basolateral NHE1 influences HCO3−absorption by regulating apical NHE3 activity. In microperfused rat MTALs, the addition of 1 nM aldosterone rapidly decreased HCO3−absorption by 30%. This inhibition was unaffected by three maneuvers that inhibit basolateral Na+/H+exchange and was preserved in MTALs from NHE1 knockout mice, ruling out the involvement of NHE1. In contrast, exposure to aldosterone for 15 min caused a 30% decrease in apical Na+/H+exchange activity over the intracellular pH range from 6.5 to 7.7, due to a decrease in Vmax. Inhibition of HCO3−absorption by aldosterone was not affected by 0.1 mM lumen Zn2+or 1 mM lumen DIDS, arguing against the involvement of an apical H+conductance or apical K+-HCO3−cotransport. These results demonstrate that aldosterone inhibits HCO3−absorption in the MTAL through inhibition of apical NHE3, and identify NHE3 as a target for nongenomic regulation by aldosterone. Aldosterone may influence a broad range of epithelial transport functions important for extracellular fluid volume and acid-base homeostasis through direct regulation of this exchanger.
Bipolar assembly of caveolae in retinal pigment epithelium
Authors: Mora Rosalia C. , Bonilha Vera L. , Shin Bo-Chul , Hu Jane , Cohen-Gould Leona , Bok Dean , Rodriguez-Boulan Enrique
Published: October 2005

Caveolae and their associated structural proteins, the caveolins, are specialized plasmalemmal microdomains involved in endocytosis and compartmentalization of cell signaling. We examined the expression and distribution of caveolae and caveolins in retinal pigment epithelium (RPE), which plays key roles in retinal support, visual cycle, and acts as the main barrier between blood and retina. Electron microscopic observation of rat RPE, in situ primary cultures of rat and human RPE and a rat RPE cell line (RPE-J) demonstrated in all cases the presence of caveolae in both apical and basolateral domains of the plasma membrane. Caveolae were rare in RPE in situ but were frequent in primary RPE cultures and in RPE-J cells, which correlated with increased levels in the expression of caveolin-1 and -2. The bipolar distribution of caveolae in RPE is striking, as all other epithelial cells examined to date (liver, kidney, thyroid, and intestinal) assemble caveolae only at the basolateral side. This might be related to the nonpolar distribution of both caveolin-1 and 2 in RPE because caveolin-2 is basolateral and caveolin-1 nonpolar in other epithelial cells. The bipolar localization of plasmalemmal caveolae in RPE cells may reflect specialized roles in signaling and trafficking important for visual function.
De novo emergence of insulin-stimulated glucose uptake in human aortic endothelial cells incubated with high glucose
Authors: Gosmanov Aidar R. , Stentz Frankie B. , Kitabchi Abbas E.
Published: October 2005

Elevated glucose concentrations have profound effects on cell function. We hypothesized that incubation of human aortic endothelial cells (HAEC) with high glucose increases insulin signaling and develops the appearance of insulin-stimulated glucose uptake by the cells. Compared with 5 mM glucose, incubation of HAEC with 30 mM glucose for up to 48 h increased in a time-dependent manner expression of insulin receptor, insulin receptor substrate (IRS)-1, IRS-2, and GLUT1 proteins. High glucose also increased the specific binding of125I-labeled insulin in HAEC accompanied by accelerated production of interleukin (IL)-6 and IL-8. Short-term stimulation by 50 μU/ml insulin did not activate [14C]glucose uptake by HAEC incubated in 5 mM glucose. However, an addition of insulin to high glucose-exposed endothelial cells led to a significant increase in [14C]glucose uptake in a glucose concentration- and time-dependent fashion, reaching a plateau at 48 h of incubation. Furthermore, incubation of HAEC with 30 mM glucose resulted in a new insulin-stimulated extracellular signal-regulated kinase-1/2 mitogen-activated protein kinase phosphorylation and increased lipid peroxidation and production of reactive oxygen species. These studies show for the first time that high glucose increases expression of insulin receptors and downstream elements of the insulin-signaling pathway and transforms “insulin-resistant” aortic endothelial cells into “insulin-sensitive” tissue regarding glucose uptake.
Differential induction of PPAR-γ by luminal glutamine and iNOS by luminal arginine in the rodent postischemic small bowel
Authors: Sato N. , Moore F. A. , Kone B. C. , Zou L. , Smith M. A. , Childs M. A. , Moore-Olufemi S. , Schultz S. G. , Kozar R. A.
Published: October 2005

Using a rodent model of gut ischemia-reperfusion (I/R), we have previously shown that the induction of inducible nitric oxide synthase (iNOS) is harmful, whereas the induction of heme oxygenase 1 (HO-1) and peroxisome proliferator-activated receptor-γ (PPAR-γ) is protective. In the present study, we hypothesized that the luminal nutrients arginine and glutamine differentially modulate these molecular events in the postischemic gut. Jejunal sacs were created in rats at laparotomy, filled with either 60 mM glutamine, arginine, or magnesium sulfate (osmotic control) followed by 60 min of superior mesenteric artery occlusion and 6 h of reperfusion, and compared with shams. The jejunum was harvested for histology or myeloperoxidase (MPO) activity (inflammation). Heat shock proteins and iNOS were quantitated by Western blot analysis and PPAR-γ by DNA binding activity. In some experiments, rats were pretreated with the PPAR-γ inhibitor G9662 or with the iNOS inhibitor N-[3(aminomethyl)benzyl]acetamidine (1400W). iNOS was significantly increased by arginine but not by glutamine following gut I/R and was associated with increased MPO activity and mucosal injury. On the other hand, PPAR-γ was significantly increased by glutamine but decreased by arginine, whereas heat shock proteins were similarly increased in all experimental groups. The PPAR-γ inhibitor G9662 abrogated the protective effects of glutamine, whereas the iNOS inhibitor 1400W attenuated the injurious effects of arginine. We concluded that luminal arginine and glutamine differentially modulate the molecular events that regulate injurious I/R-mediated gut inflammation and injury. The induction of PPAR-γ by luminal glutamine is a novel protective mechanism, whereas luminal arginine appears harmful to the postischemic gut due to enhanced expression of iNOS.
Adenosine and hypoxic dilation of rat coronary small arteries: roles of the ATP-sensitive potassium channel, endothelium, and nitric oxide
Authors: Lynch F. M. , Austin C. , Heagerty A. M. , Izzard A. S.
Published: October 2005

The aims of the study were to examine the roles of the ATP-sensitive potassium (KATP) channel, the endothelium, and nitric oxide (NO) in the responses of rat coronary small arteries to adenosine and hypoxia. Segments of rat coronary vessel were investigated in vitro using pressure myography; all vessels studied developed stable spontaneous myogenic tone during equilibration. Glibenclamide (a KATP channel inhibitor) reversed pinacidil but not 2-deoxyglucose-induced dilation. Both adenosine and hypoxia dilated the vessels, and glibenclamide did not reverse these responses. Endothelial removal or NG-nitro-l-arginine methyl ester (l-NAME) inhibited the dilation to adenosine by ∼50%; subsequent addition of glibenclamide was without effect. Hypoxic dilation was completely inhibited by endothelium removal or l-NAME. We conclude that adenosine- and hypoxia-induced dilation of rat coronary arteries does not appear to involve the KATP channel. Adenosine-induced dilation is partially and hypoxic dilation is completely dependent on endothelium-derived NO.
Cyclic ADP ribose-mediated Ca2+signaling in mediating endothelial nitric oxide production in bovine coronary arteries
Authors: Zhang Guo , Teggatz Eric G. , Zhang Andrew Y. , Koeberl Matthew J. , Yi Fan , Chen Li , Li Pin-Lan
Published: October 2005

The present study tested the hypothesis that cyclic ADP ribose (cADPR) serves as a novel second messenger to mediate intracellular Ca2+mobilization in coronary arterial endothelial cells (CAECs) and thereby contributes to endothelium-dependent vasodilation. In isolated and perfused small bovine coronary arteries, bradykinin (BK)-induced concentration-dependent vasodilation was significantly attenuated by 8-bromo-cADPR (a cell-permeable cADPR antagonist), ryanodine (an antagonist of ryanodine receptors), or nicotinamide (an ADP-ribosyl cyclase inhibitor). By in situ simultaneously fluorescent monitoring, Ca2+transient and nitric oxide (NO) levels in the intact coronary arterial endothelium preparation, 8-bromo-cADPR (30 μM), ryanodine (50 μM), and nicotinamide (6 mM) substantially attenuated BK (1 μM)-induced increase in intracellular [Ca2+] by 78%, 80%, and 74%, respectively, whereas these compounds significantly blocked BK-induced NO increase by about 80%, and inositol 1,4,5-trisphosphate receptor blockade with 2-aminethoxydiphenyl borate (50 μM) only blunted BK-induced Ca2+-NO signaling by about 30%. With the use of cADPR-cycling assay, it was found that inhibition of ADP-ribosyl cyclase by nicotinamide substantially blocked BK-induced intracellular cADPR production. Furthermore, HPLC analysis showed that the conversion rate of β-nicotinamide guanine dinucleotide into cyclic GDP ribose dramatically increased by stimulation with BK, which was blockable by nicotinamide. However, U-73122, a phospholipase C inhibitor, had no effect on this BK-induced increase in ADP-ribosyl cyclase activity for cADPR production. In conclusion, these results suggest that cADPR importantly contributes to BK- and A-23187-induced NO production and vasodilator response in coronary arteries through its Ca2+signaling mechanism in CAECs.
Impaired NO-dependent inhibition of store- and receptor-operated calcium entry in pulmonary vascular smooth muscle after chronic hypoxia
Authors: Jernigan Nikki L. , Broughton Brad R. S. , Walker Benjimen R. , Resta Thomas C.
Published: October 2005

We have recently demonstrated that chronic hypoxia (CH) attenuates nitric oxide (NO)-mediated decreases in pulmonary vascular smooth muscle (VSM) intracellular free calcium concentration ([Ca2+]i) and promotes NO-dependent VSM Ca2+ desensitization. The objective of the current study was to identify potential mechanisms by which CH interferes with regulation of [Ca2+]i by NO. We hypothesized that CH impairs NO-mediated inhibition of store-operated (capacitative) Ca2+ entry (SOCE) or receptor-operated Ca2+ entry (ROCE) in pulmonary VSM. To test this hypothesis, we examined effects of the NO donor, spermine NONOate, on SOCE resulting from depletion of intracellular Ca2+ stores with cyclopiazonic acid, and on UTP-induced ROCE in isolated, endothelium-denuded, pressurized pulmonary arteries (213 ± 8 μm inner diameter) from control and CH (4 wk at 0.5 atm) rats. Arteries were loaded with fura-2 AM to continuously monitor VSM [Ca2+]i. We found that the change in [Ca2+]i associated with SOCE and ROCE was significantly reduced in vessels from CH animals. Furthermore, spermine NONOate diminished SOCE and ROCE in vessels from control, but not CH animals. We conclude that NO-mediated inhibition of SOCE and ROCE is impaired after CH-induced pulmonary hypertension.
Simultaneous determination of the kinetics of cardiac output, systemic O2 delivery, and lung O2 uptake at exercise onset in men
Authors: Lador Frédéric , Azabji Kenfack Marcel , Moia Christian , Cautero Michela , Morel Denis R. , Capelli Carlo , Ferretti Guido
Published: October 2005

We tested whether the kinetics of systemic O2 delivery (Q̇aO2) at exercise start was faster than that of lung O2 uptake (V̇o2), being dictated by that of cardiac output (Q̇), and whether changes in Q̇ would explain the postulated rapid phase of the V̇o2 increase. Simultaneous determinations of beat-by-beat (BBB) Q̇ and Q̇aO2, and breath-by-breath V̇o2 at the onset of constant load exercises at 50 and 100 W were obtained on six men (age 24.2 ± 3.2 years, maximal aerobic power 333 ± 61 W). V̇o2 was determined using Grønlund's algorithm. Q̇ was computed from BBB stroke volume (Qst, from arterial pulse pressure profiles) and heart rate ( fh, electrocardiograpy) and calibrated against a steady-state method. This, along with the time course of hemoglobin concentration and arterial O2 saturation (infrared oximetry) allowed computation of BBB Q̇aO2. The Q̇, Q̇aO2 and V̇o2 kinetics were analyzed with single and double exponential models. fh, Qst, Q̇, and V̇o2 increased upon exercise onset to reach a new steady state. The kinetics of Q̇aO2 had the same time constants as that of Q̇. The latter was twofold faster than that of V̇o2. The V̇o2 kinetics were faster than previously reported for muscle phosphocreatine decrease. Within a two-phase model, because of the Fick equation, the amplitude of phase I Q̇ changes fully explained the phase I of V̇o2 increase. We suggest that in unsteady states, lung V̇o2 is dissociated from muscle O2 consumption. The two components of Q̇ and Q̇aO2 kinetics may reflect vagal withdrawal and sympathetic activation.