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Results for “Spatial heterogeneity”

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PubMedDate not supplied

Calcium oscillations in endothelial cells.

Several different types of endothelial cells are now known to respond to agonist stimulation with oscillations of cytosolic free [Ca2+] ([Ca2+]i). The oscillations can be repetitive [Ca2+]i spikes or sinusoidal-like oscillations according to the type of endothelial cell. Several properties of these oscillations are described including the effect of removal of extracellular Ca2+ and of changes in membrane potential, and the spatial heterogeneity of the oscillations. Results obtained with human umbilical vein endothelial cells are assessed in relation to a model for [Ca2+]i oscillations that involves Ca(2+)-induced Ca2+ release. In some preparations the oscillations are synchronized in neighbouring cells, whereas in other preparations they are not. The degree of synchrony may have functional implications and this is discussed with respect to control of blood flow and transmural permeability. A third functional implication of oscillations, their possible effect on desensitization, is also discussed.

Animals↗

PubMed1987

Modification of the radiation induced damage by 2-deoxy-D-glucose in organ cultures of human cerebral gliomas.

Effects of a glucose antimetabolite, 2-deoxy-D-glucose (2-DG), on the gamma ray induced radiation damage have been studied in organ cultures of human cerebral gliomas. Percentage of cells with micronuclei (M-fraction) was used to assay the radiation damage. Experimental data indicate the following results. Untreated cerebral gliomas show considerable spatial heterogeneity in M-fraction; In spite of this heterogeneity, increases in M-fraction induced by gamma rays can be clearly observed, if multiple and randomly selected explants are analyzed for each group; The radiation induced M-fraction in different gliomas varies over a wide range; Presence of 2-DG (5 mM) for 4 h after irradiation leads to an increase in the radiation induced M-fraction in the majority of tumors, while in a smaller number (congruent to 25%) a decrease is observed under similar conditions. These results can be explained on the basis of a model postulating differential effects of 2-DG on the energy linked modulations of the processes of repair and fixation of DNA damage, which competitively influence the formation of micronuclei.

Brain Neoplasms↗

PubMedDate not supplied

19F 2-FDG NMR imaging of the brain in rat.

Images of the rat head reflecting glucose utilization were obtained using 2-fluoro-2-deoxy-D-glucose (2-FDG) and 19F nuclear magnetic resonance (NMR) imaging. Spatial heterogeneity of glucose utilization in the rat head was clearly demonstrated showing significantly higher glucose utilization in the brain as compared to the surrounding tissues. Although the potential adverse effects of the high doses of 2-FDG (400 mg/kg) needed to perform the study preclude immediate application of this technique to clinical quantitative glucose utilization studies, the present study shows potential for future development of glucose utilization imaging by NMR.

Animals↗

PubMed1994

Magnetic resonance imaging (MRI) of calcium alginate gels.

The spatial heterogeneity of calcium alginate gels has been visualised by the variation of image intensity across the gel by one-, two-, and three-dimensional MRI. From the linear dependence of (T2)-1 on alginate concentration it is now possible to use MRI to map alginate concentration gradients within calcium alginate gels noninvasively. Since the concentration of alginate determines the pore size of the gel matrix, those alginate concentration maps will be useful in determining the pore size distribution within the gel, which is important in controlled release applications.

Alginates↗

PubMed1992

Temporal and spatial modulation of a cytoskeletal antigen during peripheral axonal pathfinding.

A neuron-specific cytoskeletal antigen (5E10), whose expression pattern during initial motoneuron outgrowth into the chick limb suggests that it is playing a role in axon guidance, is described. This antigen, which was shown to be a phosphorylated epitope, probably of the intermediate weight neurofilament protein (NF-M), exhibits a highly stereotyped and spatially heterogeneous pattern of expression. The point of onset of expression, which was abrupt and occurred in the distal axon and base of the growth cone, differed between groups of neurons that projected to different targets. Specifically, expression occurred from positions where previous perturbation experiments suggested that the axons in question would begin responding to specific guidance cues, and it remained high along the axon from this point to the target. Expression of this antigen could also be induced in cultured motoneurons by activating several second messenger systems.

Animals↗

PubMed1996

Recent developments in theories of pathogenesis of AIDS.

Experimental and theoretical progress in HIV research includes an improved resolution of the spatial heterogeneity and the dynamics (time course and turnover rates) of virus and CD4+ cells. Some of these advances have resulted from the joint work of experimental and theoretical groups, demonstrating that interdisciplinary research can be fruitful.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Vasa vasorum neovascularization and lesion distribution among different vascular beds in ApoE-/-/LDL-/- double knockout mice.

OBJECTIVE: To increase understanding of the substantial variation in the incidence and distribution of atherosclerotic lesions among different vascular beds. In view of some evidence that there are different distributions of adventitial vasa vasorum (VV) in different vascular beds, and that this correlates with lesion formation, we explored this possible linkage in apoE-/-/LDL-/- double knockout mice, which develop VV at age beyond 16 weeks. METHODS AND RESULTS: Samples from the aorta, coronary, pulmonary, carotid, and cerebral arteries in apoE-/-/LDL-/- double knockout mice at the age of 16-80 weeks (n=24) were scanned by micro-CT. Using those 3D images, we characterized plaque volume, vessel luminal diameter and VV luminal volume along the vessels. Results were complemented by histology. Advanced atherosclerotic lesions were found in the aorta, pulmonary artery and carotid artery. Occluded intramyocardial vessels (vessel diameter approximately 0.1mm) with concomitant myocardial infarctions were found without any evidence of adventitial VV neovascularization. VV luminal volume follows the order: aorta>pulmonary arteries>carotid arteries. VV were only observed in atherosclerotic diseased vessels with a lumen diameter>0.4mm. No atherosclerotic lesions, and no VV, were observed in cerebral arteries. CONCLUSION: The spatial heterogeneity in the development of atherosclerotic lesions among different vascular beds is linked to appearance of VV and to vessel lumen diameter.

Animals↗

PubMed2006

High throughput assessment of cells and tissues: Bayesian classification of spectral metrics from infrared vibrational spectroscopic imaging data.

Vibrational spectroscopy allows a visualization of tissue constituents based on intrinsic chemical composition and provides a potential route to obtaining diagnostic markers of diseases. Characterizations utilizing infrared vibrational spectroscopy, in particular, are conventionally low throughput in data acquisition, generally lacking in spatial resolution with the resulting data requiring intensive numerical computations to extract information. These factors impair the ability of infrared spectroscopic measurements to represent accurately the spatial heterogeneity in tissue, to incorporate robustly the diversity introduced by patient cohorts or preparative artifacts and to validate developed protocols in large population studies. In this manuscript, we demonstrate a combination of Fourier transform infrared (FTIR) spectroscopic imaging, tissue microarrays (TMAs) and fast numerical analysis as a paradigm for the rapid analysis, development and validation of high throughput spectroscopic characterization protocols. We provide an extended description of the data treatment algorithm and a discussion of various factors that may influence decision-making using this approach. Finally, a number of prostate tissue biopsies, arranged in an array modality, are employed to examine the efficacy of this approach in histologic recognition of epithelial cell polarization in patients displaying a variety of normal, malignant and hyperplastic conditions. An index of epithelial cell polarization, derived from a combined spectral and morphological analysis, is determined to be a potentially useful diagnostic marker.

Bayes Theorem↗

PubMed2006

Electrical behavior and pore accumulation in a multicellular model for conventional and supra-electroporation.

Extremely large but very short (20 kV/cm, 300 ns) electric field pulses were reported recently to non-thermally destroy melanoma tumors. The stated mechanism for field penetration into cells is pulse characteristic times faster than charge redistribution (displacement currents). Here we use a multicellular model with irregularly shaped, closely spaced cells to show that instead overwhelming pore creation (supra-electroporation) is dominant, with field penetration due to pores (ionic conduction currents) during most of the pulse. Moreover, the model's maximum membrane potential (about 1.2 V) is consistent with recent experimental observations on isolated cells. We also use the model to show that conventional electroporation resulting from 100 microsecond, 1 kV/cm pulses yields a spatially heterogeneous electroporation distribution. In contrast, the melanoma-destroying pulses cause nearly homogeneous electroporation of cells and their nuclear membranes. Electropores can persist for times much longer than the pulses, and are likely to be an important mechanism contributing to cell death.

Biophysics↗

PubMed2006

Heavy ion radiation up-regulates Cx43 and ameliorates arrhythmogenic substrates in hearts after myocardial infarction.

OBJECTIVE: Radiation has been shown to enhance intercellular communication in the skin and lungs through an increase of connexin43 (Cx43) expression. If analogous Cx43 up-regulation is induced in the diseased heart, it would provide a new perspective in radiation therapy for arrhythmias. The aim of the present study is to test this hypothesis. METHODS: Non-transmural myocardial infarction (MI) was created in 24 rabbits by microsphere injection into the coronary arteries. Twenty-four rabbits without MI were used as controls. Targeted external heavy ion beam irradiation (THIR; 15 Gy) was applied 2 weeks after MI with an accelerator (HIMAC, Chiba, Japan). RESULTS: The THIR was associated with an increase of Cx43 mRNA and protein levels in the left ventricle in control as well as in MI rabbits. THIR also increased lateralization of Cx43, which was no longer colocalized with cadherins. In MI hearts, immunoreactive Cx43 signals were reduced in the peri-infarct zone, and the reduction was reversed by THIR. In-vivo epicardial potential mapping on the free wall (64 unipolar electrodes to cover 7 x 7 mm) in MI hearts revealed reduced conduction velocity, whereas dispersion of the activation-recovery interval (ARI) was increased compared with controls, and these changes were reversed by THIR. The vulnerability for ventricular tachyarrhythmias (VT/VF), which was estimated by programmed stimulation, was increased in MI hearts, and this increased vulnerability to arrhythmias was reversed by THIR. CONCLUSIONS: THIR increases Cx43 expression, improves the conductivity, decreases the spatial heterogeneity of repolarization, and reduces the vulnerability of rabbit hearts to ventricular arrhythmias after MI. THIR could have an antiarrhythmic potential through an improvement of electrical coupling.

Animals↗

PubMed2004

Depolarisation and repolarisation sequences of ventricular epicardium in chickens (Gallus gallus domesticus).

Activation and recovery sequences were mapped by means of 64-channel synchronous recording of extracellular potentials on ventricular epicardium in chickens. Ventricular epicardium was depolarized due to multiple breakthroughs. The recovery of ventricular epicardium occurs from the apex to the base of heart and does not repeat the activation sequence. Gradients of repolarisation exist over the ventricular epicardium in birds. Repolarisation pattern of ventricular epicardium depends primarily on intrinsic spatial heterogeneities of ARIs over epicardium.

Action Potentials↗

PubMed2005

The homeodomain transcription factor Irx5 establishes the mouse cardiac ventricular repolarization gradient.

Rhythmic cardiac contractions depend on the organized propagation of depolarizing and repolarizing wavefronts. Repolarization is spatially heterogeneous and depends largely on gradients of potassium currents. Gradient disruption in heart disease may underlie susceptibility to fatal arrhythmias, but it is not known how this gradient is established. We show that, in mice lacking the homeodomain transcription factor Irx5, the cardiac repolarization gradient is abolished due to increased Kv4.2 potassium-channel expression in endocardial myocardium, resulting in a selective increase of the major cardiac repolarization current, I(to,f), and increased susceptibility to arrhythmias. Myocardial Irx5 is expressed in a gradient opposite that of Kv4.2, and Irx5 represses Kv4.2 expression by recruiting mBop, a cardiac transcriptional repressor. Thus, an Irx5 repressor gradient negatively regulates potassium-channel-gene expression in the heart, forming an inverse I(to,f) gradient that ensures coordinated cardiac repolarization while also preventing arrhythmias.

Action Potentials↗

PubMed2006

A hybrid vector for ligand-directed tumor targeting and molecular imaging.

Merging tumor targeting and molecular-genetic imaging into an integrated platform is limited by lack of strategies to enable systemic yet ligand-directed delivery and imaging of specific transgenes. Many eukaryotic viruses serve for transgene delivery but require elimination of native tropism for mammalian cells; in contrast, prokaryotic viruses can be adapted to bind to mammalian receptors but are otherwise poor vehicles. Here we introduce a system containing cis-elements from adeno-associated virus (AAV) and single-stranded bacteriophage. Our AAV/phage (AAVP) prototype targets an integrin. We show that AAVP provides superior tumor transduction over phage and that incorporation of inverted terminal repeats is associated with improved fate of the delivered transgene. Moreover, we show that the temporal dynamics and spatial heterogeneity of gene expression mediated by targeted AAVP can be monitored by positron emission tomography. This new class of targeted hybrid viral particles will enable a wide range of applications in biology and medicine.

Animals↗

PubMed2025

Association of Lung Quantitative CT Scan Textures With Systemic Inflammation and Mortality in COPD.

BACKGROUND: COPD is characterized by persistent inflammation that is responsible for remodeling the bronchovascular bundles (BVBs), which may lead to poor quality of life. Quantitative CT (QCT) scan textures of the lung can capture local disease patterns of inflammation and related respiratory morbidity. RESEARCH QUESTION: Are BVB textures, obtained from the adaptive multiple feature method, associated with systemic inflammation, morbidity, and mortality in COPD? STUDY DESIGN AND METHODS: We analyzed data from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS; n = 2,981) and the Genetic Epidemiology of COPD (COPDGene) study (n = 10,305). The predictors included 2 QCT scan biomarkers, the BVB and CT density gradient (CTDG) textures, age, sex, BMI, race, smoking status, pack-years of smoking, CT scan-detected emphysema, and square root of the wall area of a hypothetical airway with a 10-mm lumen perimeter (Pi10). Outcomes included plasma biomarker concentrations from Meso Scale Discovery proteomics assays and CBC counts, both as markers of inflammation, along with FEV1, FEV1 to FVC ratio, St. George's Respiratory Questionnaire score, 6-minute walk distance, and modified Medical Research Council dyspnea scale score. Associations of these QCT scan textures with FEV1 decline and all-cause mortality also were investigated. RESULTS: Increased BVB texture was associated significantly with elevated neutrophil and monocyte counts and the neutrophil to lymphocyte ratio, independent of clinical covariates, CT scan-detected emphysema, and Pi10. Elevated CTDG was associated with increased neutrophil count, NLR, and tumor necrosis factor α. Increased CTDG and BVB textures also were associated with a lower FEV1 and 6-minute walk distance. CTDG at baseline was also associated with decline in FEV1 at the 5-year follow-up in the COPDGene study. We observed a significant association of both BVB texture (SPIROMICS: hazard ratio [HR], 1.084 [95% CI, 1.035-1.135; P < .001]; COPDGene: HR, 1.106 [95% CI, 1.080-1.131; P < .001]) and CTDG texture (SPIROMICS: HR, 1.033 [95% CI, 1.003-1.064; P = .03]; COPDGene: HR, 1.079 [95% CI, 1.061-1.096; P < .001]) with all-cause mortality independent of CT scan-detected emphysema and Pi10. INTERPRETATION: QCT scan textures may provide imaging evidence of the spatial heterogeneity of lung inflammation and overall disease burden in COPD. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; Nos.: NCT01969344 (SPIROMICS) and NCT00608764 (COPDGene); URL: www. CLINICALTRIALS: gov.

Humans↗

PubMed2004

Travelling-wave analysis of a model of the immune response to cancer.

In this paper we present a travelling-wave analysis of a mathematical model describing the growth of a solid tumour in the presence of an immune system response. From a modelling perspective, attention is focused upon the attack of tumour cells by tumour infiltrating cytotoxic lymphocytes (TICLs), in a small multicellular tumour, without necrosis and at some stage prior to (tumour-induced) angiogenesis. As we have shown in previous work, for a particular choice of parameters, the underlying reaction-diffusion-chemotaxis system of partial differential equations is able to simulate the well-documented phenomenon of cancer dormancy by depicting spatially heterogeneous tumour cell distributions that are characterized by a relatively small total number of tumour cells. This behaviour is consistent with several immunomorphological investigations. Moreover, the alteration of certain parameters of the model is enough to induce bifurcations into the system, which in turn result in tumour invasion in the form of a standard travelling wave. The work presented in this paper complements the bifurcation analysis undertaken by Matzavinos et al. [Math. Med. Biol. IMA 21 (2004) 1-34] and establishes the existence of travelling-wave solutions for the system under discussion by promoting the understanding of the geometry of an appropriate phase space.

Humans↗

PubMed2006

Competing selfish genetic elements in the butterfly Hypolimnas bolina.

Maternally inherited selfish genetic elements are common in animals . Whereas host genetics and ecology are recognized as factors that may limit the incidence of these parasites , theory suggests one further factor-interference with other selfish elements-that could affect their prevalence . In this paper, we show that spatial heterogeneity in the occurrence of the male-killing Wolbachia wBol1 in the tropical butterfly Hypolimnas bolina is caused by a second infection that can exclude the male-killer. We first provide evidence of a second Wolbachia strain, wBol2, present in most populations that do not carry the male-killer but rare or absent when the male-killer is present. Crossing data indicate that wBol2 in males induces cytoplasmic incompatibility to both uninfected and wBol1-infected females. The wBol2 infection can therefore not only spread through uninfected populations but also resist invasion by wBol1. Thus, we provide empirical support for the hypothesis that the incidence of particular selfish genetic elements can limit the presence of competing types.

Animals↗

PubMed2005

Dynamic contrast-enhanced magnetic resonance imaging: a non-invasive method to evaluate significant differences between malignant and normal tissue.

PURPOSE: An ever recurring challenge in diagnostic radiology is the differentiation between non-malignant and malignant tissue. Based on evidence that microcirculation of normal, non-malignant tissue differs from that of malignant tissue, the goal of this study was to assess the reliability of dynamic contrast-enhanced Magnetic Resonance Imaging (dcMRI) for differentiating these two entities. MATERIALS AND METHODS: DcMRI data of rectum carcinoma and gluteus maximus muscles were acquired in 41 patients. Using an fast T1-mapping sequence on a 1.5-T whole body scanner, T1-maps were dynamically retrieved before, during and after constant rate i.v. infusion of a contrast medium (CM). On the basis of the acquired data sets, PI-values were calculated on a pixel-by-pixel basis. The relevance of spatial heterogeneities of microcirculation was investigated by relative frequency histograms of the PI-values. RESULTS: A statistically significant difference between malignant and normal tissue was found for the mean PI-value (P < 0.001; 8.95 ml/min/100 g +/- 2.45 versus 3.56 ml/min/100 g +/- 1.20). Additionally relative frequency distributions of PI-values with equal class intervals of 2.5 ml/min/100 g revealed significant differences between the histograms of muscles and rectum carcinoma. CONCLUSION: We could show that microcirculation differences between malignant and normal, non-malignant tissue can be reliably assessed by non-invasive dcMRI. Therefore, dcMRI holds great promise in the aid of cancer assessment, especially in patients where biopsy is contraindicated.

Adenocarcinoma↗

PubMed2005

Impacts of sewage irrigation on heavy metal distribution and contamination in Beijing, China.

A potential hazard to Beijing was revealed due to the accumulation trend of heavy metals in agricultural soils with sewage irrigation, which results in metal contamination and human exposure risk. Samples including soils and plants were collected to assess the impacts of sewage irrigation on the irrigated farming area of Beijing. Concentrations of the five elements Cd, Cr, Cu, Zn, and Pb were determined in samples to calculate the accumulation factor and to establish a basis for environmental protection and the suitability of sewage irrigation for particular land use in the urban-rural interaction area of Beijing. Using reference values provided by the Beijing Background Research Cooperative Group in the 1970s, the pollution load index (PLI), enrichment factor (EF), and contamination factor (CF) of these metals were calculated. The pollution load indices (sewage irrigation land 3.49) of soils indicated that metal contamination occurred in these sites. The metal enrichment (EF of Cd 1.8, Cr 1.7, Cu 2.3, Zn 2.0, Pb 1.9) and the metal contamination (CF of Cd 2.6, Cr 1.5, Cu 2.0, Zn 1.7, Pb 1.6) showed that the accumulation trend of the five toxic metals increased during the sewage irrigation as compared with the lower reference values than other region in China and world average, and that pollution with Cd, Cu, Zn, and Pb was exacerbated in soils. The distributions of these metals were homogeneous in the irrigation area, but small-scale heterogeneous spatial distribution was observed. Irrigation sources were found to affect heavy metal distributions in soils. It was suggested that heavy metal transfer from soils to plants was a key pathway to human health exposure to metal contamination. However, with the expansion of urban areas in Beijing, soil inhalation and ingestion may become important pathways of human exposure to metal contamination.

Agriculture↗