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PubMed1999

A study of the solar effect on actinic keratoses by quantification of elastic fibres using an image analysis system.

It is widely accepted that elastotic changes of the skin are primarily an indicator of cumulative sun exposure of the dermis and are a characteristic finding of actinic keratoses. To date, there have been few reports that measure the amount of elastic tissue objectively and quantitatively, especially in actinic keratoses. The computerized image analysis method has proved useful recently in determining the area of elastic fibres. Using this method, we objectively quantified the elastotic tissue in actinic keratoses and evaluated the relationship between the degree of dermal elastosis, epidermal atypia and histological types of actinic keratoses. Of the 28 actinic keratoses studied, the average percentage area of the elastic fibre was 40.48 +/- 14.48 (mean +/- SD) percentile. There was a 3.65-fold increase in the amount of elastic fibre in actinic keratoses compared with that of seborrhoeic keratoses occurring on the face (p < 0.00001). In addition, the more severe the atypia, the greater the area of elastic fibres in a representative section of the dermis. In conclusion, we observed that on quantitative assessment of elastic tissue in actinic keratoses, the percentage area of the elastic fibres in a representative section of the dermis ranges from 34.86 to 46.11%. This result may provide information for use in histological diagnosis of actinic keratoses and evidence for the possible role of sunlight in the pathogenesis of actinic keratosis.

Adult↗
PubMed1990

Elastic filaments in skeletal muscle revealed by selective removal of thin filaments with plasma gelsolin.

Muscle needs an elastic framework to maintain its mechanical stability. Removal of thin filaments in rabbit skeletal muscle with plasma gelsolin has revealed the essential features of elastic filaments. The selective removal of thin filaments was confirmed by staining with phalloidin-rhodamine for fluorescence microscopy, examination of arrowhead formation with myosin subfragment 1 by electron microscopy, and analysis by SDS-PAGE. Thin section electron microscopy revealed the elastic fine filaments (approximately 4 nm in diameter) connecting thick filaments and the Z line. After removal of thin filaments, both rigor stiffness and active tension generation were lost, but the resting tension remained. These observations indicate that the thin filament-free fibers maintain a framework composed of the serial connections of thick filaments, the elastic filaments, and the Z line, which gives passive elasticity to the contractile system of skeletal muscle. The resting tension that remained in the thin filament-free fibers was decreased by mild trypsin treatment. The only protein component that was digested in parallel with the decrease in the resting tension and the disappearance of the elastic filaments was alpha-connectin (also called titin 1), which was transformed from the alpha to the beta form (from titin 1 to 2, respectively). Thus, we conclude that the main protein component of the elastic filaments is alpha-connectin (titin 1).

Actin Cytoskeleton↗
PubMed1966

The fine structure of elastic fibers.

The fine structure of developing elastic fibers in bovine ligamentum nuchae and rat flexor digital tendon was examined. Elastic fibers were found to contain two distinct morphologic components in sections stained with uranyl acetate and lead. These components are 100 A fibrils and a central, almost amorphous nonstaining area. During development, the first identifiable elastic fibers are composed of aggregates of fine fibrils approximately 100 A in diameter. With advancing age, somewhat amorphous regions appear surrounded by these fibrils. These regions increase in prominence until in mature elastic fibers they are the predominant structure surrounded by a mantle of 100 A fibrils. Specific staining characteristics for each of the two components of the elastic fiber as well as for the collagen fibrils in these tissues can be demonstrated after staining with lead, uranyl acetate, or phosphotungstic acid. The 100 A fibrils stain with both uranyl acetate and lead, whereas the central regions of the elastic fibers stain only with phosphotungstic acid. Collagen fibrils stain with uranyl acetate or phosphotungstic acid, but not with lead. These staining reactions imply either a chemical or an organizational difference in these structures. The significance and possible nature of the two morphologic components of the elastic fiber remain to be elucidated.

Acetates↗
PubMed2005

Elasticities in variable environments: properties and implications.

Elasticities in stochastic matrix models are used to understand both population and evolutionary dynamics. We examine three such elasticities: stochastic elasticity E(ij)(S) with respect to the (i, j) matrix element, the elasticity E(ij)(S mu) with respect to the mean mu(ij) of the matrix element, and the elasticity E(ij)(S sigma) with respect to the variability sigma(ij) of the matrix element. We show that the stochastic elasticity E(S) does not accurately describe the effect of variability; one should use E(S sigma) and E(S mu). We establish two general properties of these elasticities: a sum rule that connects them and a limit on the sum of the E(S sigma). We discuss the implications of these properties for the analysis of buffering and selection on the average rates versus the variability of rates.

Ecosystem↗
PubMed2002

Quantitative elasticity imaging: what can and cannot be inferred from strain images.

We examine the inverse problem associated with quantitative elastic modulus imaging: given the equilibrium strain field in a 2D incompressible elastic material, determine the elastic stiffness (shear modulus). We show analytically that a direct formulation of the inverse problem has no unique solution unless stiffness information is known a priori on a sufficient portion of the boundary. This implies that relative stiffness images constructed on the assumption of constant boundary stiffness are in error, unless the stiffness is truly constant on the boundary. We show further that using displacement boundary conditions in the forward incompressible elasticity problem leads to a nonunique inverse problem. Indeed, we give examples in which exactly the same strain field results from different elastic modulus distributions under displacement boundary conditions. We also show that knowing the stress on the boundary can, in certain configurations, lead to a well-posed inverse problem for the elastic stiffness. These results indicate what data must be taken if the elastic modulus is to be reconstructed reliably and quantitatively from a strain image.

Computer Simulation↗
PubMed2006

Fibulin-5 mutations: mechanisms of impaired elastic fiber formation in recessive cutis laxa.

To elucidate the molecular mechanisms of impaired elastic fiber formation in recessive cutis laxa, we have investigated two disease-causing missense substitutions in fibulin-5, C217R and S227P. Pulse-chase immunoprecipitation experiments indicated that S227P mutant fibulin-5 was synthesized and secreted by skin fibroblasts at a reduced rate when compared with the wild-type protein. Both mutants failed to be incorporated into elastic fibers by transfected rat lung fibroblasts. Purified recombinant fibulin-5 with either mutation showed reduced affinity for tropoelastin in solid-phase binding assays. Furthermore, S227P mutant fibulin-5 also showed impaired association with fibrillin-1 microfibrils. The same mutation triggered an endoplasmic reticulum (ER) stress response, as indicated by the strong co-localization of this mutant protein with folding chaperones in the ER, including calreticulin, immunoglobulin-binding protein and protein disulfide isomerase, and by increased rates of apoptosis in patient fibroblasts. Histological analysis of skin sections from a cutis laxa patient with a homozygous S227P mutation showed a lack of fibulin-5 in the extracellular matrix and a concomitant disorganization of dermal elastic fibers. By electron microscopy, elastic fibers in the skin of this patient showed a failure of elastin globules to fuse into a continuous elastic fiber core. We conclude that recessive cutis laxa mutations in fibulin-5 result in misfolding, decreased secretion and a reduced interaction with elastin and fibrillin-1 leading to impaired elastic fiber development. These findings support the hypothesis that fibulin-5 is necessary for elastic fiber formation by facilitating the deposition of elastin onto a microfibrillar scaffold via direct molecular interactions.

Amino Acid Substitution↗
PubMed2003

Biopolymer Chain Elasticity: A novel concept and a least deformation energy principle predicts backbone and overall folding of DNA TTT hairpins in agreement with NMR distances.

A new molecular modelling methodology is presented and shown to apply to all published solution structures of DNA hairpins with TTT in the loop. It is based on the theory of elasticity of thin rods and on the assumption that single-stranded B-DNA behaves as a continuous, unshearable, unstretchable and flexible thin rod. It requires four construction steps: (i) computation of the tri-dimensional trajectory of the elastic line, (ii) global deformation of single-stranded helical DNA onto the elastic line, (iii) optimisation of the nucleoside rotations about the elastic line, (iv) energy minimisation to restore backbone bond lengths and bond angles. This theoretical approach called 'Biopolymer Chain Elasticity' (BCE) is capable of reproducing the tri-dimensional course of the sugar-phosphate chain and, using NMR-derived distances, of reproducing models close to published solution structures. This is shown by computing three different types of distance criteria. The natural description provided by the elastic line and by the new parameter, Omega, which corresponds to the rotation angles of nucleosides about the elastic line, offers a considerable simplification of molecular modelling of hairpin loops. They can be varied independently from each other, since the global shape of the hairpin loop is preserved in all cases.

Biopolymers↗
PubMed2006

Indirect readout: detection of optimized subsequences and calculation of relative binding affinities using different DNA elastic potentials.

Essential biological processes require that proteins bind to a set of specific DNA sites with tuned relative affinities. We focus on the indirect readout mechanism and discuss its theoretical description in relation to the present understanding of DNA elasticity on the rigid base pair level. Combining existing parametrizations of elastic potentials for DNA, we derive elastic free energies directly related to competitive binding experiments, and propose a computationally inexpensive local marker for elastically optimized subsequences in protein-DNA co-crystals. We test our approach in an application to the bacteriophage 434 repressor. In agreement with known results we find that indirect readout dominates at the central, non-contacted bases of the binding site. Elastic optimization involves all deformation modes and is mainly due to the adapted equilibrium structure of the operator, while sequence-dependent elasticity plays a minor role. These qualitative observations are robust with respect to current parametrization uncertainties. Predictions for relative affinities mediated by indirect readout depend sensitively on the chosen parametrization. Their quantitative comparison with experimental data allows for a critical evaluation of DNA elastic potentials and of the correspondence between crystal and solution structures. The software written for the presented analysis is included as Supplementary Data.

Base Pairing↗
PubMed2000

Esmolol-induced regional wall motion abnormalities do not affect regional ventricular elastances.

UNLABELLED: The effect of regional wall motion abnormalities (RWMA) on regional and global left ventricular (LV) elastances has not been defined. To induce RWMA, we infused esmolol (9 mg) into the left anterior descending coronary artery in eight anesthetized open-chest canine preparations. Global and regional stroke volumes and end-systolic pressure-volume relationships (LV conductance catheter) and pressure-length relationships (sonomicrometer crystals) were measured in dysfunctional (apical) and normal (basilar) LV regions at baseline, during esmolol infusion, and after treatment with a systemic dobutamine infusion (4 microg. kg(-1). min(-1)) and combined dobutamine-esmolol. Esmolol induced apical dyskinesis, as evidenced by reduced effective apical stroke volumes and stroke work, a parallel right-shift of the apical regional, global end-systolic pressure-volume relationships, and increased regional and global LV volumes (P < 0.05). However, global and regional elastances remained unchanged. Dobutamine increased global and apical regional elastances, but did not increase regional volumes. During the infusion of combined esmolol-dobutamine, apical elastance and volumes increased compared with baseline (P < 0.05), but apical regional stroke work decreased. Thus, esmolol-induced RWMA were associated with cardiac dilation but not with decreased regional or global elastances. IMPLICATIONS: Regional and global elastances and maximal stroke volumes may not identify esmolol-induced left ventricular regional dysfunction in dogs. The primary effect of asynchrony of regional contraction is global cardiac dilation. Systemic dobutamine infusion increases regional and global left ventricular elastances but does not reverse regional wall motion abnormality-induced cardiac dilation.

Animals↗
PubMed2002

Elastance correlates with outcome after endoscopic third ventriculostomy in adults with hydrocephalus caused by primary aqueductal stenosis.

OBJECTIVE: To study prospectively the correlation between clinical outcome after endoscopic third ventriculostomy (ETV) and resistance to the outflow of cerebrospinal fluid (R(out)) and elastance in adults with hydrocephalus caused by primary aqueductal stenosis (AS). METHODS: R(out) and elastance were measured in the subarachnoid space and intraventricularly before ETV in 15 consecutive patients. Three months after the ETV, the clinical effect was evaluated by standardized indices, and R(out) and elastance were measured. If symptoms persisted and the ETV was patent, shunt surgery was offered. The effect of the shunt operation and R(out) were measured after 3 months. RESULTS: Four patients experienced excellent improvement, six improved slightly, and five had unchanged or deteriorated symptoms after ETV. R(out) before ETV did not correlate with outcome. R(out) decreased after ETV with correlation to the clinical effect; in the six patients who had shunt surgery, R(out) decreased further. High preoperative elastance correlated strongly with a good outcome and reduction of ventricle size. Elastance did not change after ETV. CONCLUSION: R(out) intraventricularly and in the subarachnoid space could not predict the outcome of the ETV, but the reduction in R(out) correlated positively with clinical improvement. Preoperative elastance correlated positively with clinical improvement, and elastance was unchanged after ETV. Clinical improvement correlated positively with reduction in ventricle size.

Adolescent↗
PubMed2005

Nonaffine correlations in random elastic media.

Materials characterized by spatially homogeneous elastic moduli undergo affine distortions when subjected to external stress at their boundaries, i.e., their displacements from a uniform reference state grow linearly with position , and their strains are spatially constant. Many materials, including all macroscopically isotropic amorphous ones, have elastic moduli that vary randomly with position, and they necessarily undergo nonaffine distortions in response to external stress. We study general aspects of nonaffine response and correlation using analytic calculations and numerical simulations. We define nonaffine displacements as the difference between and affine displacements, and we investigate the nonaffinity correlation function and related functions. We introduce four model random systems with random elastic moduli induced by locally random spring constants (none of which are infinite), by random coordination number, by random stress, or by any combination of these. We show analytically and numerically that scales as where the amplitude is proportional to the variance of local elastic moduli regardless of the origin of their randomness. We show that the driving force for nonaffine displacements is a spatial derivative of the random elastic constant tensor times the constant affine strain. Random stress by itself does not drive nonaffine response, though the randomness in elastic moduli it may generate does. We study models with both short- and long-range correlations in random elastic moduli.

Biophysics↗
PubMed2004

Detection of lumen-intima interface of posterior wall for measurement of elasticity of the human carotid artery.

In our series of studies on noninvasive assessment of the regional elasticity of the arterial wall, the displacement gradient (change in thickness) of the arterial wall caused by the heartbeat was measured by the phased-tracking method. Because the displacement gradient corresponds to the strain due to the change in blood pressure, the elasticity can be evaluated from the displacement gradient of the arterial wall and the blood pressure, which are noninvasively measured at the upper arm. In the measurement of the elasticity of the arterial wall by our method, the region in which the elastic modulus is estimated must be assigned beforehand; currently, the lumen-intima boundary of the arterial wall is manually determined by the operator. For the real-time measurement of the elasticity of the arterial wall, a fast, automated method is necessary for detection of the boundary. In this paper, a cost function is proposed for differentiation of the arterial wall from the lumen. The proposed cost function was applied to ultrasound data, which were noninvasively obtained for five human carotid arteries. In comparison with the case of detection using only the amplitude of the echo, the root mean square error between the automatically detected lumen-intima boundary and the manually assigned boundary was significantly improved by using the proposed cost function. Furthermore, the lumen-intima boundary was automatically detected in a short period. Such a method is required for real-time measurement of the elasticity of the arterial wall, though detection of the outer boundary of the adventitia, which is not described in this paper, is also necessary to realize real-time elasticity measurement by our method.

Adult↗
PubMed1982

Studies in cutaneous aging: I. The elastic fiber network.

We studied by light and electron microscopy the elastic fibers in he sun exposed and sun protected skin of normal and psoriatic individuals of different ages in order to separate the changes of actinic damage from those of chronological aging. The sun exposed skin showed 2 types of elastic fiber abnormalities-one related to actinic damage and the other to chronological aging. The sun protected buttock skin showed only the latter. From ages 30 to 70, a minority of the elastic fibers exhibited abnormalities that appeared to represent a process of fiber disintegration. After age 70, the majority of elastic fibers showed these abnormalities. These abnormalities were present without accompanying inflammatory cells. Also, there was morphological evidence of continuing synthesis of elastic fibers during the lifetime of these subjects, except that from ages 50-93, the fibers appeared to be loosely, rather than compactly, assembled. Incubation of dermal slices from buttock skin of young adults with porcine pancreatic elastase and bovine chymotrypsin produced elastic fiber degradation that closely simulated the changes that were observed in aged sun protected skin. We propose that one of the features of cutaneous aging is a slow, spontaneous, progressive degradative process inherent in the elastic fiber that can be enzymatically accelerated from decades to hours by elastase and chymotrypsin.

Adolescent↗
PubMed1995

Measurement of skin elastic properties with a new suction device (I): Relationship to age, sex and the degree of obesity in normal individuals.

We measured skin elastic properties (distension ability, retraction ability, and the skin elasticity) of 4 different body sites, finger, hand, forearm, and chest, in 191 normal individuals by means of a new suction device and investigated the correlation of skin elastic properties with sex, site, age, and the degree of obesity. Neither sex nor the degree of obesity were correlated with skin elastic properties. The skin elastic property of the chest was significantly higher than those of the other three sites. Decrease in the skin elasticity of the hand, forearm and chest were associated with aging. This simple and non-invasive device can provide an objective method for evaluating skin elastic property.

Adolescent↗
PubMed1995

Histomorphometric parameters and susceptibility to neutrophil elastase degradation of skin elastic fibres from healthy individuals and patients with Marfan syndrome, Ehlers-Danlos type IV, and pseudoxanthoma elasticum.

The morphometric parameters of mid-dermal elastic fibres from the skin of four patients with Marfan syndrome, four patients with Ehlers-Danlos syndrome type IV (EDS IV), and two patients with pseudoxanthoma elasticum (PXE) were determined, and compared with those of healthy individuals of a similar age range. The volume fraction occupied by elastic fibres was significantly reduced in Marfan patients compared with normal controls, and this was independent of age. In contrast, it was significantly increased in PXE patients, whereas the volume fraction occupied by skin elastic fibres varied within the EDS IV group. Dermal elastic fibres from patients with Marfan syndrome, EDS IV and PXE are hydrolysed by human neutrophil elastase in a qualitatively and quantitatively different fashion from those from healthy individuals. Marfan syndrome and EDS IV dermal elastic fibres were found to be more resistant to hydrolysis by human neutrophil elastase, but PXE elastic fibres were hydrolysed at a rate similar to elastic fibres from control skin.

Adolescent↗
PubMed1989

Abnormal elastic fibers in elastosis of breast carcinoma. Ultrastructural and immunohistochemical studies.

Elastosis in benign and malignant breast lesions was studied by light microscopic immunohistochemistry for elastin and by electron microscopy. Upon immunohistochemical examination for elastin, elastosis, particularly in scirrhous-type ductal carcinoma, showed two characteristic staining patterns: fibrously and intensely stained elastic fibers and evenly stained elastic masses. Elastic fibers showing increased fibrous staining occurred mainly in the stromal areas, and were considered to be newly formed because they consisted of tannic acid-positive amorphous components and abundant microfibrils. Evenly stained elastic masses were observed mainly in the periductal areas and showed less intense stainability. These masses consisted of numerous fine amorphous components with plentiful microfibrils. In some regions within these masses, there were condensed accumulations of irregularly arranged small amorphous components associated with only a few microfibrils. These amorphous components had an ill-defined outline and were occasionally associated with spiralling collagen fibrils and cell debris. On the basis of these findings, the periductal evenly stained elastic masses were thought to be formed by excessive production of elastic fibers and degradation of pre-existing and newly formed elastic fibers.

Breast Neoplasms↗
PubMed2006

Regional variations in the density and arrangement of elastic fibres in the anulus fibrosus of the human lumbar disc.

Elastic fibres are critical components of the extracellular matrix in dynamic biological structures that undergo extension and recoil. Their presence has been demonstrated in the anulus fibrosus of the human lumbar intervertebral disc; however, a detailed regional analysis of their density and arrangement has not been undertaken, limiting our understanding of their structural and functional roles. In this investigation we have quantitatively described regional variations in elastic fibre density in the anulus fibrosus of the human L3-L4 intervertebral disc using histochemistry and light microscopy. Additionally, a multiplanar comparison of patterns of elastic fibre distribution in the intralamellar and interlamellar zones was undertaken. Novel imaging techniques were developed to facilitate the visualization of elastic fibres otherwise masked by dense surrounding matrix. Elastic fibre density was found to be significantly higher in the lamellae of the posterolateral region of the anulus than the anterolateral, and significantly higher in the outer regions than the inner, suggesting that elastic fibre density in each region of the anulus is commensurate with the magnitude of the tensile deformations experienced in bending and torsion. Elastic fibre arrangments in intralamellar and interlamellar zones were shown to be architecturally distinct, suggesting that they perform multiple functional roles within the anulus matrix structural hierarchy.

Adolescent↗
PubMed2005

Relationships between lung function, smoking and morphology of dermal elastic fibres.

OBJECTIVE: To investigate the relationship between lung function and dermal elastic fibres in non-smokers and smokers with and without chronic obstructive pulmonary disease (COPD). METHOD: A cross-sectional study was performed with lung function as the outcome [forced expiratory volume in the first second (FEV1)%, FEV1/forced vital capacity (FVC)% and residual volume (RV)/total lung capacity (TLC)%] and smoking (pack-years) and morphology of dermal elastic fibres (fibres/mm(2) and percentage histologic field filled with them) as independent variables, with assessment of the associations between these variables by univariate and multivariate testing. RESULTS: Sixty outpatients reporting chronic cough and/or phle\gm were enrolled (16 non-smokers/44 smokers; COPD: 26, 43.3%). Both lung function and elastic fibres in the reticular dermis (fibres/mm(2)r(s) = 0.36, percentage of the histologic field filled by elastic fibres r(s) = 0.48, P < or = 0.01) correlated with cumulative smoking (Spearman's rank correlation coefficient). Lung function parameters correlated with percentage of the histologic field filled by elastic fibres (FEV1%: r = -0.43; FEV1/FVC%: r = -0.36 and RV/TLC%: r = 0.43; P < or = 0.01, Pearson correlation coefficient), and COPD was significantly related to this morphologic parameter (odds ratio 1.26, 95% confidence interval 1.06-1.48; P = 0.006), associations that depended mainly on cumulative smoking. CONCLUSION: Lung function impairment with an obstructive pattern is associated with morphologic abnormalities in the reticular dermis appearing in the histologic section as an increase in the percentage of the field filled by elastic fibres. This relationship depends on cumulative smoking and suggests a common effect of smoking on the elastic fibres in both lung and skin.

Adult↗