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Elastosis in breast carcinoma: I. Immunohistochemical characterization of elastic fibres.

Elastosis associated with invasive ductal and lobular carcinomas of the breast was examined by tinctorial and immunohistochemical staining methods, enzyme digestion, and electron microscopy. The elastotic material exhibited the tinctorial staining properties of elastic fibres, and the ultrastructural appearances were those of elastic fibres although there was a higher proportion of microfibrils than in normal mature elastic fibres. The elastosis was immunostained by antisera to human fetal elastin, lysozyme and amyloid P component, as in other sites where elastic fibres are found. These findings indicate that immunohistochemically intact elastic fibres are present in the elastosis of breast cancer. They also demonstrate that lysozyme and amyloid P component are co-distributed with elastic fibres in elastosis of breast carcinoma, as distinct components with different susceptibilities to enzyme digestion. The cellular origin of elastosis in breast carcinoma remains uncertain.

Actin Cytoskeleton↗

Structural biology of the fibres of the collagenous and elastic systems.

The different types of fibres of the collagenous and elastic systems can be demonstrated specifically in tissue sections by comparing the typical ultrastructural picture of each of the fibre types with studies using selective staining techniques for light microscopy. A practical modus operandi, which includes the recommended staining procedures and interpretation of the results, is presented. Micrographs and tables are provided to summarize the differential procedures. Reticulin fibres display a distinct argyrophilia when studied by means of silver impregnation techniques, and show up as a thin meshwork of weakly birefringent, greenish fibres when examined with the aid of the Picrosirius-polarization method. In addition, electron-microscopic studies showed that reticulin fibres are composed of a small number of thin collagen fibrils, contrasting with the very many thicker fibrils that could be localized ultrastructurally to the sites where non-argyrophilic, coarse collagen fibres had been characterized by the histochemical methods used. The three different fibre types of the elastic system belong to a continuous series: oxytalan-elaunin-elastic (all of the fibre types comprising collections of microfibrils with, in the given sequence, increasing amounts of elastin). The three distinct types of elastic system fibres have different staining characteristics and ultrastructural patterns. Ultrastructurally, a characteristic elastic fibre consists of two morphologically different components: a centrally located solid cylinder of amorphous and homogeneous elastin surrounded by tubular microfibrils. An oxytalan fibre is composed of a bundle of microfibrils, identical to the elastic fibre microfibrils, without amorphous material. In elaunin fibres, dispersed amorphous material (elastin) is intermingled among the microfibrils.

Animals↗

Titin elasticity in the context of the sarcomere: force and extensibility measurements on single myofibrils.

Skeletal-muscle titin contains in its I-band section two main elastic elements, stretches of Ig-like domains and the PEVK segment. Both elements contribute to the extensibility and passive force development of relaxed skeletal muscle fibers during stretch. To explore the nature of elasticity of the segments, their force-extension relation was determined with immunofluorescence and immunoelectron microscopy, combined with isolated myofibril mechanics. The results were then fitted with recent models of biopolymer elasticity. Whereas an entropic-spring mechanism may account for the elasticity of the Ig-domain segments, PEVK-titin elasticity appears to have both entropic and enthalpic origins. The modeling explains why the two elements extend sequentially upon stretch: elongation of the Ig-domain regions (with folded modules) is followed by unraveling of the PEVK domain. I-band titin in cardiac muscle is expressed in two main isoforms, N2-A and N2-B. The N2-A isoform is similar to that found in skeletal muscle, whereas the N2-B titin is distinguished by cardiac-specific Ig-motifs and nonmodular sequences within the central I-band section. By examining the extensibility of N2-B titin, it was found that this isoform extends by recruiting three distinct elastic elements: poly-Ig regions and the PEVK domain at low to modest stretch, and in addition, a unique 572-residue sequence insertion at higher physiological stretch. Extension of all three elements allows cardiac titin to stretch fully reversibly at physiological sarcomere lengths, without the need to unfold individual Ig domains.

Animals↗

Histochemistry of elastic and related fibres in the human eye in health and disease.

Although the presence of mature elastic fibres in the sclera, trabecular meshwork and Bruch's membrane of the human eye has been recognized for many years, it is only latterly that the existence of the elastic-related fibres oxytalan and elaunin has been appreciated. The microfibrillar component of elastic, oxytalan, which is present in several ocular structures in infancy, can either mature to fully-developed elastic tissue or, as in the cornea, disappear in subsequent years. Deposition of elastic fibres, particularly the incomplete forms, can occur in the post-developmental period in a variety of disease states but the stimulus and functional significance in most situations is obscure. The evidence suggests, however, that the capacity to form elastic-related tissue is not confined to any one cell type.

Contractile Proteins↗

Elastic fibers in the tunica propria of the seminiferous tubules. Light and electron microscopic investigations.

Histological examination of numerous biopsies from mature testes, repeatedly showed irregularities of the elastin staining in the tunica propria of the seminiferous tubules. Even when abundant elastic fibers were visible by light microscopy, no elastic fibers were demonstrable in the electron microscope in ultrathin sections of testicular tubules embedded in Epon and contrasted with phosphotungstic acid (PTA). In 43 biopsies from 22 men aged 17-39 years (19 investigations of sterility and three patients with hypogonadotropic hypogonadism) we therefore checked for the occurrence of elastic fibers in the wall of the seminiferous tubules. Matrix loci of elastic fibers could indeed by demonstrated by electron microscopy using PTA and potassium permanganate (KMnO4), but only after embedding in araldite. Under these conditions, light and electron microscopic findings agreed with each other. The appearances of moderate and severe testicular tubular atrophy differed slightly from one another with regard to the amount of elastin. In the "Sertoli cells only syndrome", elastic fibers were demonstrable only outside the hyalinized inner layer. In the Klinefelter syndrome, only "uncertain" elastin loci were present, but greatly increased microfibrils were to be seen using the electron microscope. No elastic elements and only very sparse microfibrils were present in the tunica propria of the tubules of young men with hypogonadotropic hypogonadism.

Adolescent↗

Predictive control of grip force when moving object with an elastic load applied on the arm.

Skilled object manipulation relies on the capability to adjust the grip force according to the consequences of our movements in terms of the resulting load force of the object. Such predictive grip force control requires (at least) two neural processes: (1) predicting the kinematic characteristics of the unfolding arm trajectory and (2) predicting the load force on the object resulting, among other factors, from the arm movement. The goal of this study was to examine whether subjects can still anticipate the resulting load force on the object when the moving arm is submitted to a type of load that does not contribute to the object load. To this end, 12 subjects were asked to rhythmically move a 0.4 kg object under three different conditions. In the first condition (ARM), an elastic cord was attached to the upper arm. In the second condition, the elastic cord was attached to the object (OBJECT). In the third condition, the elastic cord was absent (NO ELAST). At the kinematic level, results showed no influence of the elastic cord on the pattern of movement of the object. At the kinetic level, cross-correlation analyses between grip force and load force acting on the object revealed significant correlations with minimal delays. In addition, grip force profiles were similar under the ARM and NO ELAST conditions, both differing from the OBJECT condition. Overall, we interpret these results as evidence that the neural processes involved in the prediction of the arm trajectory and those involved in the prediction of the load on the object held can take into account different external force fields, thereby preserving the functionality of the behaviour.

Adult↗

Effect of a hypergravity environment on cortical bone elasticity in rats.

There is considerable interest in determining whether hypergravity can be used as a countermeasure for microgravity-induced bone loss. This study was conducted on 20 immature male rats in order to investigate possible elastic adaptations of cortical bone in rapidly growing rats exposed to chronic hypergravity. Ten rats were continuously centrifuged for 14 days at twice gravitational acceleration (2G) on a 12.75 foot radius centrifuge and 10 rats concurrently acted as stationary controls. The effect of hypergravity on the elastic characteristics of cortical bone was quantified via ultrasonic wave propagation. Propagation velocities of longitudinal and shear waves were measured through cubic cortical specimens from the posterior femoral diaphyses. Density was measured with an Archimedes' technique. The orthotropic elastic properties were calculated and used to compare the difference between groups. Results showed an average increase in both the Young's moduli (Eii, + 2.2%) and shear moduli (Gij, + 4.3%) with a statistically significant increase only in G12 (+15.7%, P = 0.046). The ratio of transverse to axial strain (Poisson's ratio, nuij) demonstrated statistically significant changes in nu12, nu21, nu13, and nu31 (P < 0.05). These findings suggest that although slight elastic changes were incurred via a hypergravity environment, the treatment level or duration in this study do not dramatically perturb the normal elastic behavior of cortical bone and that dramatic biomechanical differences noted in previous studies were due more to structural changes than material elasticity changes. Hypergravity applied post facto to a microgravity environment would offer further illucidation of this method as treatment for a degenerative spaceflight experience.

Animals↗

Cytokine release from marrow mononuclear cells is negatively correlated to cortical elasticity in non-osteoporotic postmenopausal women.

Activation of bone remodeling is likely to be under the control of mechanical factors acting, in part, through soluble local factors. We therefore investigated a relationship between cytokine production by marrow cells and bone elasticity. We studied 36 non-osteoporotic postmenopausal women undergoing hip arthroplasty for hip arthrosis (mean age: 68 +/- 8 years; lumbar BMD Z-score: +0.54 +/- 0.33 SD). Adherent marrow mononuclear cells were cultured for 48 hours with autologous plasma, and supernatants were harvested for PGE2, IL-1, TNF-alpha, and IL-6 measurements. Femoral neck cortical bones were removed during surgery for cortical histomorphometric evaluation and determination of elasticity indices (C33) using ultrasonic transmission method. In this nonosteoporotic population, femoral neck longitudinal elasticity indices were inversely correlated to both cortical thickness (r = -0.58, P < 0.01) and cortical porosity (r = -0.33, P < 0.01). The longitudinal elasticity indices were also negatively correlated to basal IL-1 and TNF-alpha release by adherent mononuclear marrow cells (r = -0.59, P < 0.01; r = -0.60, P < 0.01, respectively). However, no relationship was found between the three cytokines tested and either cortical thickness or porosity. These data show a link between cortical biomechanical properties and local factors involved in bone remodeling. We suggest that increased bone elasticity decreases transmission of strain, which in turn decreases cytokine release from marrow cells. However, whether cytokines influence bone elasticity or vice versa remains to be demonstrated.

Aged↗

Ultrasound velocity of trabecular cubes reflects mainly bone density and elasticity.

Studies have indicated that quantitative ultrasound (QUS) variables may be influenced by the mechanical properties of bone which in turn are determined by bone's material and structural properties. However, from these studies it is unclear what role density, elasticity, and structure play in determining velocity. Eighteen defatted, 12-mm cubic trabecular bone specimens were cut from cadaveric specimens. Amplitude-dependent speed of sound (SOS) using a single point QUS system was assessed in three orthogonal axes. Magnetic resonance images were obtained, from which measures of apparent trabeuclar structure were derived. The specimens were nondestructively tested in compression along three orthogonal axes defined by the sides of the cubes. The elastic modulus (in the three directions) and the strength (in one direction) were determined. Trabecular BMD was measured by quantitative computed tomography. SOS varied significantly with direction of measurement, with the highest value in the axial direction (axial:1715 m/s, sagittal: 1662 m/second, and coronal: 1676 m/s). SOS of each of the three axes was generally associated with the various mechanical (r = 0.30-0.87), density (r = 0.81-0.93), and bone structural variables (0.3-0.8). However, after adjusting the SOS correlations by density, only the correlation with elasticity remained significant in the coronal direction. BMD alone explained 88-93% of variance in SOS whereas in the multivariate model, BMD plus elasticity and/or anisotropic variables explained 96-98% of the variance in SOS. Variability of SOS is explained mostly by density and to a small extent by elasticity or anisotropy. Since only 2-6% of the variance of the QUS measurement is not explained by density and elasticity, one could conclude that the remaining variance reflects other properties of bone or perhaps simply measurement error. Evidence that these other properties may be structure related is only found in the anisotropy of QUS parameter.

Adult↗

Decrease of elastic tissue fibres in stem villus blood vessels of the human placenta during IUGR and IUGR with concomitant pre-eclampsia.

In a recent study we described an increase of elastic tissue fibres in blood vessel walls of placental stem villi during pre-eclampsia when compared to uncomplicated pregnancies. Furthermore, the thickness of these blood vessel walls was enhanced in pre-eclampsia. Since it is known that elastic tissue fibres increase in systemic hypertension, it may be assumed that the enhancement of elastic tissue fibres in placental stem villi during pre-eclampsia may be induced by the hypertension. To get further insight into this assumption, we examined the amount of elastic tissue fibres in stem villus blood vessels of placentae of pregnancies complicated by intrauterine growth retardation (isolated IUGR, fourteen cases), a disease without hypertension of the mother and such with pre-eclampsia and concomitant IUGR (IUGR+PE, nine cases). Each study group was compared with uncomplicated pregnancies (twenty-six cases). Unfixed cryostat serial sections were processed for conventional orcein staining and for the demonstration of alpha-actin-immunoreactivity. The intensity of orcein staining of stem villus blood vessel walls was evaluated by a semiquantitative score method. Significant lower intensities of orcein staining were calculated for blood vessel walls of placentae of isolated IUGR (P=0.0007) and IUGR+PE (P=0.0039) when compared to uncomplicated pregnancies each. Additionally, the blood vessel wall thickness of stem villi of isolated IUGR (P=0.0081) and IUGR+PE (P=0.0007) was significantly reduced. In comparison to the above mentioned investigation, our results show that, in contrast to isolated pre-eclampsia, elastic tissue fibres are decreased during pregnancies complicated by IUGR, independently of the occurrence of concomitant pre-eclampsia when compared to uncomplicated pregnancies. From our studies it may be considered that the increase of elastic tissue fibres in placentae of patients with isolated pre-eclampsia may be induced by systemic hypertension. Furthermore, our study underline arguments that IUGR may be an independent disease of the fetus.

Adult↗

The subserosal elastic lamina: an anatomic landmark for stratifying pT3 colorectal cancer.

PURPOSE: Approximately 50 percent of all patients with resected colorectal carcinoma have tumors with pT3 status; however, no subclassifications of the penetration depth have been proposed. The purpose of this study is to evaluate the significance of histologic invasion beyond subserosal elastic lamina by colorectal carcinoma for postoperative recurrence and long-term survival after resection. METHODS: pT3 colorectal carcinomas located above the peritoneal reflection were retrospectively classified into two depth grades (subserosal elastic lamina classification). Namely, "pT3-shallow" is defined as tumors those are confined above the subserosal elastic lamina, and "pT3-deep" is defined as tumors those penetrate beyond it. Based on subserosal elastic lamina classification, the 325 consecutive patients who underwent resections were divided into two groups, and then the clinicopathologic features, incidence of postoperative recurrence, and survival rates were compared between the two groups. RESULTS: The overall postoperative recurrence rate in the pT3-deep group (35.2 percent) was higher than that in the pT3-shallow group (20.8 percent). In detail, liver and peritoneal recurrence rates in the pT3-deep group (19.7 percent, 7.7 percent, respectively) were higher than those in the pT3-shallow group (9.4 percent, 2.0 percent, respectively). There was a strong difference ( P < 0.0001) in overall survival rate between the pT3-deep group (5-year survival of 57.0 percent) and the pT3-shallow group (5-year survival of 78.6 percent). Multivariate analysis revealed that synchronous hematogenous metastasis ( P < 0.0001), lymph node metastasis ( P < 0.05), venous invasion ( P < 0.01), and subserosal elastic lamina classification ( P < 0.05) were the independent prognostic factors for postoperative survival. CONCLUSIONS: The newly proposed subserosal elastic lamina classification is a useful subclassification to predict the prognosis of patients with resected pT3 colorectal carcinomas.

Aged↗

Distribution of elastic fibres in the developing rabbit craniomandibular joint.

The biomechanical properties of the CMJ disc depend upon the composition and organization of the extracellular matrix. Elastic fibres are important elements of the matrix and may be in part responsible for the resilience of the disc during jaw movements. Elastic fibres first appeared after the establishment of a miniature CMJ at 23 days of prenatal development. The first elastic fibres appeared in the antero-inferior and postero-inferior attachment regions of the disc. In the newborn rabbit there were elastic fibres in the articulating surfaces of the joint and by one week fibres could be seen in the intermediate zone portion of the disc. At two weeks, when the animals were beginning to experiment with solid food, the disc band areas showed accumulations of elastic fibres and proteoglycans. The findings suggest that the elastic elements of the disc, squamosal and condylar articulations may have a resilience function which develops in response to functional loads placed upon the joint as the rabbit grows and changes diet.

Aging↗

The orientation of fibroblasts and neutrophils on elastic substrata.

The reaction of fibroblasts to the elastic properties of the substratum was studied using elastic collagen films. These films were stretched in one axis to give a substratum which was anisotropic in its elasticity and deformability. Analysis of the orientation of fibroblasts cultured on these substrata showed that they oriented along the axis of stretch which was also the axis of fibre alignment. This orientation was significantly reduced when the films were made less elastic by attachment to a glass slide and chemical fixation. Neither of these procedures appeared to alter the surface shape of these films, which suggests that the elastic properties of the substratum markedly influence the orientation of fibroblasts. The orientation of locomotion of neutrophil leukocytes on elastic collagen films was also analysed and no bias along the axis of stretch was observed. This was compared with neutrophil locomotion in 3-D stretched collagen gels, in which a strong bias along the axis of stretch and of fibre alignment was observed. The possible reasons for the response of these two cell types is discussed.

Animals↗

Effect of thiouracil upon canine arterial elastic tissue.

Unlike some other mammalian species, the dog is relatively resistant to the development of elevated levels of serum cholesterol after prolonged cholesterol feeding. This may be overcome by suppressing thyroid activity with thiouracil. Information regarding possible activity of thiouracil itself upon the arterial tissues is almost nonexistent. The present investigation was undertaken to test whether this drug has any such action, especially upon the arterial elastic tissues. Destructive changes were observed in arterial elastic tissues in dogs given thiouracil for three and six months. The changes consisted of accentuation of the elastic fibrillar components, formation and subsequent coalescence of clefts, and fragmentation and ultimate "dissolution" of the elastic elements. The results suggest that thiouracil may exert a damaging effect upon the arterial elastic fibers; thus, it is possible that one of the mechanisms by which thiouracil and cholesterol administration induces experimental atherosclerosis in the dog is by elastic tissue destruction, possibly promoting the subsequent lipid accumulation in the arterial wall.

Animals↗

Elastic moduli, yield stress, and ultimate stress of cancellous bone in the canine proximal femur.

Elastic moduli, yield stress and ultimate compressive stress were determined for cancellous bone from the femoral head and neck regions of the canine femur. Unconfined compression tests were performed on 5 mm cubic samples which were cut from two femurs. Elastic moduli were measured in three orthogonal directions, and the yield stress and ultimate stress were measured along the proximal-distal axis. The results from this investigation support previous assumptions that the mechanical behavior of canine cancellous bone is qualitatively similar to human cancellous bone. The canine cancellous bone was observed to be anisotropic in elastic modulus. For two thirds of the cubic specimens tested, the elastic modulus was largest in the load-bearing, proximal-distal direction. A linear relationship between yield stress and elastic modulus was observed for canine bone, as is typical of human bone. A similar linear relationship between ultimate stress and elastic modulus was observed. Thus, for canine bone as well as for human bone, failure appears to be governed by a strain level which is position independent. The yield strain of 0.0259 and ultimate strain of 0.0288 for canine bone were both less than the yield strain of 0.0395 reported for human bone.

Animals↗

Properties of the tendinous structures and series elastic component of EDL muscle-tendon complex of the rat.

Characteristics of the entire series elastic component and of tendinous structures separately (tendon and aponeurosis) were compared for rat EDL muscle-tendon complex during isometric contractions, to study the contribution of tendinous structures to series elastic component characteristics. Compliance of series elastic component was measured using quick length decreases during the force plateau of isometric contractions. Lengths of tendinous structures were measured using macro-photographs during passive and active muscle conditions. Length data obtained from aponeurosis showed inconsistency with respect to elastic behaviour in two ways: the difference of aponeurosis length in active muscle at short length and at optimum length exceeded the extension of series elastic component for the same force range. Furthermore, aponeurosis in passive muscle at optimum length was considerably longer than in active muscle at short length, despite the fact that muscle force in the former condition is smaller than in the latter. It is concluded that aponeurosis length does not depend exclusively on force but is also muscle length-dependent. This muscle length dependence was not found for tendon of EDL. Additional experiments showed that series elastic component compliance does not depend on muscle length. It is concluded that muscle length-dependent changes of aponeurosis length-force characteristics involve shifts of its force length curve to other aponeurosis lengths.

Animals↗

Elastic wave propagation in bone in vivo: methodology.

The purpose of this study was to investigate the usefulness of elastic wave propagation (EWP) in estimating the mechanical properties (elasticity) of human tibia. The test group was composed of 78-yr-old women assigned to high (n = 19) and low (n = 17) bone mineral density (BMD) groups as measured at the calcaneus by the 125I-photon absorption method. The EWP apparatus consisted of an impact-producing hammer with a force strain gauge and two accelerometers positioned on the bone. Results for nylon and acrylic were used to calibrate the apparatus. Polyvinyl chloride (PVC) solid rods and tubes of various diameters were used to evaluate the relationship between the elastic wave velocity and cross-sectional area. The density and the cross-sectional area of tibia were measured by the computerized tomographic (CT) method at the same intersection points as velocity recordings. The velocities in tibia of bending waves produced by the mechanical hammer were found to depend on the density, area moment of inertia, and density-dependent elastic constants of bone. It is important to account for the changes of these quantities along the bone. It is suggested that the velocity of elastic waves and various indices derived there from provide inexpensive ways of evaluating the elastic properties of bone.

Acceleration↗

Pulsatile diameter and elastic modulus of the aortic arch in essential hypertension: a noninvasive study.

A noninvasive evaluation of the aortic arch diameter was performed in 16 subjects with sustained essential hypertension and in 15 normal subjects of similar age, gender and body surface area. In all subjects, measurements were obtained of brachial mean arterial pressure and pulse pressure, cardiac mass (judged on echocardiography) and carotid-femoral pulse wave velocity together with ultrasound determinations of aortic arch diastolic and systolic diameter (suprasternal window). For each subject, pulsatile change in aortic diameter, strain and aortic arch elastic modulus were calculated. Compared with normal subjects, the hypertensive subjects showed an increase in aortic arch diameter (diastolic diameter 29.6 +/- 1.0 versus 25.4 +/- 1.0 mm, p less than 0.01), in elastic modulus (1.071 +/- 0.131 versus 0.526 +/- 0.045 10(5) N.m-2, p less than 0.001) and pulse wave velocity (11.8 +/- 0.5 versus 8.9 +/- 0.3 m/s, p less than 0.001). In the study group, a positive correlation was observed between diastolic aortic arch diameter and mean arterial pressure (r = 0.54, p less than 0.01) and between elastic modulus and cardiac mass (r = 0.60, p less than 0.01). Elastic modulus and age were positively correlated (r = 0.73, p less than 0.01) in hypertensive but not in normal subjects (r = 0.08, NS). This study is the first to demonstrate noninvasively that both the aortic arch diameter and the elastic modulus are increased in patients with sustained uncomplicated essential hypertension. These findings suggest that the increase in elastic modulus could influence the development of cardiac hypertrophy, and that both age and blood pressure act independently as factors that alter the arterial wall of subjects with sustained essential hypertension.

Adult↗