[Joint hypermobility, skin hyper-elasticity, connective tissue fragility: classical symptoms of Ehlers-Danlos syndrome].
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Dihydrotachysterol-induced aortic calcification. A histochemical and ultrastructural investigation.
Early dihydrotachysterol-induced calcification of the rat aorta occurs in elastic lamellae. The first deposition of inorganic substance leads to the formation of very thin filament-like structures of low electron density. The characteristic shape of these structures suggests that they could correspond to calcified filamentous components of the elastic tissue. When calcification spreads from the calcified elastic lamellae into the adjacent tissue, the inorganic substance is initially collected in roundish structures, probably of cellular origin, and is successively laid down in the entire matrix of the aortic wall, including collagen fibrils. All the calcified areas contain glycoproteins and acid proteoglycans. A cartilage-like tissue often develops near calcified areas. Its fine structure is very similar to that of the normal hyaline cartilage. It can be calcified, but usually the inorganic substance is not crystalline as it is in normal cartilage. It seems to consist of very small, linearly aggregated inorganic granules which form irregular structures. These seem to develop in close relationship with the fibrillar, probably collagenic, network of the matrix. No ultrastructural findings have been obtained for explaining cartilage induction near calcified areas of the aortic wall. It is possible that cartilage differentiation is regulated by diffusible substances which cannot be recognized under the electron microscope.
Animals↗
A robust numerical solution to reconstruct a globally relative shear modulus distribution from strain measurements.
To noninvasively quantify tissue elasticity for differentiating malignancy of soft tissue, we previously proposed a two-dimensional (2-D) mechanical inverse problem in which simultaneous partial differential equations (PDE's) represented the target distribution globally of relative shear moduli with respect to reference shear moduli such that the relative values could be determined from strain distributions obtained by conventional ultrasound (US) or nuclear magnetic resonance (NMR) imaging-based analysis. Here, we further consider the analytic solution in the region of interest, subsequently demonstrating that the problem is inevitably ill-conditioned in real-world applications, i.e., noise in measurement data and improper configurations of mechanical sources/reference regions make it impossible to guarantee the existence of a stable and unique target global distribution. Next, based on clarification of the inherent problematic conditions, we describe a newly developed numerical-based implicit-integration approach that novelly incorporates a computationally efficient regularization method designed to solve this differential inverse problem using just low-pass filtered spectra derived from strain measurements. To evaluate method effectiveness, reconstructions of the global distribution are carried out using intentionally created ill-conditioned models. The resultant reconstructions indicate the robust solution is highly suitable, while also showing it has high potential to be applied in the development of an effective yet versatile diagnostic tool for quantifying the distribution of elasticity in various soft tissues.
Biomechanical Phenomena↗
Airway and lung elastic fibre is not reduced in asthma nor in asthmatics following corticosteroid treatment.
By morphometric investigation of the relative content of elastic and collagen fibres, we have tested the hypothesis that loss of elastic fibres in the conducting airways and lung parenchyma may reduce tissue elastic recoil, resulting in increased airway maximal closure and apparent increased responsiveness. The study groups comprised: Group A (n = 11) with relatively mild atopic asthma using inhaled bronchodilators prn (i.e. short-term corticosteroids users); Group B (n = 9) with more severe asthma requiring inhaled bronchodilators regularly, and daily inhaled glucocorticosteroids (i.e. longterm corticosteroid users); Group C (n = 12) normal healthy workers. Bronchial biopsy samples were taken from three sites from the left lung. Group A biopsy samples were taken before and after a 4 wk treatment period with inhaled corticosteroids (200 micrograms b.i.d.) and the relative elastic and collagen fibre content of a subepithelial zone was determined from electron micrographs. In a parallel study, the relative proportion of elastic fibre in post mortem lung tissue samples (inner aspect of the bronchial wall, alveolar wall, and points of attachment of surrounding alveoli to intrapulmonary bronchi) from subjects suffering a fatal asthma attack (n = 11), and non-asthmatic suffering sudden death (n = 9), were determined using Miller's elastic and eosin counterstain for light microscopy. In bronchial biopsies of normal subjects, 4.6 (SEM 1.1)% of subepithelial connective tissue was elastic fibre, similar to mild asthmatic subjects, 1.9 (SEM 0.48)%. Neither short-term (4 weeks) inhaled corticosteroid (200 micrograms b.i.d.) nor long-term (< 6 months) treatment with variable doses of inhaled steroids (100-1000 micrograms b.i.d.) significantly altered the elastic or collagen content of the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Viscoelasticity of the vessel wall: the role of collagen and elastic fibers.
The aortic wall contains collagen fibrils, smooth muscle cells, and elastic fibers as the primary load-bearing components. It is well known that the collagen fibrils bear loads in the circumferential direction, whereas elastic fibers provide longitudinal as well as circumferential support. Stiffening of the vessel wall is associated with loss of elastic tissue and increases in the collagen content: however, little is known about the mechanism of vessel wall stiffening with age. The purpose of this review is to attempt to relate structural changes that occur to the collagen and elastic fibers to changes in the viscoelastic behavior that are associated with aging. Analysis of the viscoelastic mechanical properties of collagen fibrils from tendon, skin, and aortic wall suggest that the collagen fibrils of aortic wall are different than those of other tissues. The elastic spring constant of the collacen fibrils in vessel walls is significantly less than that found in tendon, suggesting that the presence of type III collagen in aortic wall increases the flexibility of the collagen fibrils. Furthermore, it is hypothesized that changes in the interface between collagen fibrils, elastic fibers, and smooth muscle during aging and in connective tissue disorders leads to changes in the viscoelasticity of the vessel wall.
Aorta↗
THE MICROSCOPICAL APPEARANCES OF HUMAN PERIPHERAL ARTERIES DURING GROWTH AND AGING.
Twelve peripheral arteries are described in 59 patients of all ages. Accumulation of ground substance in the media, accompanied by small foci of calcification of the internal elastic lamina, was found in the large leg arteries of young adults, and progressively in a wider series of arteries throughout life. This picture showed no relationship to hypertension, to Mönckeberg's sclerosis, or to the development of atheroma. A notable quantity of ground substance may be a feature of early intimal development, and of a thickened intima in adult life, and probably the major constituent of an organizing thrombus. Organizing thrombi were apparently incidental findings at several sites even in young adults, and showed no association with the state of the arterial wall beneath the lesion, the wall being in fact normal, though accumulated mucopolysaccharide was always present. Atheroma increases with age, and its focal incidence gives way to confluence in the arteries of the leg. Occlusive peripheral artery atheroma was found only in cases where the cause of death was severe atheroma, e.g., coronary artery disease and abdominal aortic aneurysm, or in myxoedema, in which the incidence of occlusive lesions may differ from that in severe generalized atheroma. Elastic tissue is described in all coats of the artery wall, with some variants of the common pattern. The musculo-elastic cushion is not seen after adolescence, and it is suggested that the cushion represents the growing point of the artery. Longitudinal muscle bundles are almost confined to the popliteal artery, where they may form an essential buttress for a large branching artery subject to unusual external stresses. The functions and origin of the ground substance are discussed.
Adolescent↗
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↗
Cigarette smoking-associated elastotic changes in the skin.
BACKGROUND: Clinical features of the skin in persons who smoke include increased wrinkling, gauntness, and discoloration that has been termed smoker's face. The histologic changes in the sun-exposed skin of these patients have not been previously elucidated. OBJECTIVE: The purpose of this study was to assess the amount of elastosis in the sun-exposed skin of smokers and nonsmokers. METHODS: We evaluated the skin from the forehead and cheeks of 17 smokers and 14 nonsmokers for the presence of elastosis. With the use of a computer-generated analysis of tissue sections at 4 different levels, the amount of elastotic material was expressed as an average percent of the field staining for elastic tissue. Patients were also evaluated for the presence of other malignancies, arsenic and radiation exposure, and previous skin cancers. RESULTS: There was a significantly greater amount of elastosis (P < .05) in the skin of patients who smoked compared with those patients who did not. No significant differences were found between the 2 groups with regard to the other parameters evaluated. CONCLUSION: Cigarette smoking is associated with an increase in elastosis, which may contribute to the clinical features of "smoker's face."
Elastic Tissue↗
Electrically-induced collagen calcification in pig skin. A histopathologic and histochemical study.
Deposition of calcium salts on collagen fibres in skin of fully anaesthetized pigs was induced by exposure to direct current (d.c.). In biopsies obtained from cathode areas successively from day 1 to day 7 after exposure the histopathologic and histochemical changes before and after the initial deposition of calcium salts have been examined. For comparison skin sites with intradermal injected calcium hydroxyapatite crystals were studied in addition. Small areas of calcified collagen and elastic fibres were noted in viable tissue 2 days after d.c. exposure. In succeeding days the calcified areas enlarged with new deposits always more superficial and closer to the epidermis than the original calcium deposits. Preconditions for calcification appear to be (1) a pH change in basic direction and/or the electrochemical processes specific to the cathode area and (2) a viable tissue. Elastic fibres appear to have a lower calcification threshold than collagen fibres. A positive staining for glycoproteins (PAS) and glycosaminoglycans (alcian blue pH 2.5) was noted in the calcified collagen fibres simultaneously with the calcification. In succeeding days the intensity of the staining reactions increased. Whether changes in the glycoproteins, collagen and its intimately bound glycosaminoglycans precede the calcification or the staining reactions develop secondarily to this deposition is not known. However, seven days after intradermal injections of Ca-apatite crystals in pig skin small and large crystals were observed ultrastructurally without any relation to collagen fibrils, but the calcified tissue presented a positive PAS and alcian blue reaction from day 2. Thus the PAS and alcian blue stainings in this model develop secondary to the deposition of calcium salts.
Animals↗
Architectural remodelling in acute and chronic interstitial lung disease: fibrosis or fibroelastosis?
AIMS: Pulmonary fibrosis in acute and chronic lung disease has been much investigated, but little attention has been directed at the elastic tissue in these situations. Our aim was to verify whether elastic deposition accompanies collagen deposition in the repairing process of acute and chronic lung injury. METHODS AND RESULTS: We measured, by image analysis, the content of fibres of the collagenous and elastic systems of the alveolar septum in histological slides sampled from autopsied lungs, using the picrosirius-polarization method and Weigert's resorcin-fuchsin stain, respectively. Five groups were studied: I, 10 normal patients; II, 10 patients with cardiogenic pulmonary oedema; III, 23 adult respiratory distress syndrome (ARDS) patients in the early phase; IV, 14 ARDS patients in the late fibroproliferative phase; and V, 10 idiopathic pulmonary fibrosis patients. The first two groups were used as controls. The content of fibres of the collagenous and elastic systems was significantly increased in groups IV and V as compared to the other groups. CONCLUSIONS: Our results indicate that deposition of elastic system fibres is present in the fibroproliferative phase of ARDS and in usual interstitial pneumonia and suggest that this event may contribute to the alveolar mechanical dysfunction and remodelling that occur in acute and chronic interstitial lung disease.
Acute Disease↗
Morphology of the internal elastic lamina in arteries from pulmonary hypertensive patients: a confocal laser microscopy study.
The development and progression of pulmonary hypertension lesions involve continuous remodeling of the arterial wall, including the extracellular matrix components. The integrity of the internal elastic lamina may represent a barrier to cell migration and formation of intimal proliferative lesions. Some patients with congenital cardiac shunts develop precocious intimal occlusive lesions,whereas others evolve with isolated medial hypertrophy. We studied the 2-D and 3-D morphology of the internal elastic lamina of peripheral pulmonary arteries to search for any difference regarding the type of histological lesion. Fifteen lung biopsies collected for diagnostic purposes from patients with congenital shunts and 6 control lungs (mean ages, 15.8 and 14.7 mo) were studied using the confocal laser scanning microscope, under predetermined conditions of laser intensity, brightness and contrast. We measured the thickness of the internal elastic lamina and determined the number of gaps and projections of elastic tissue towards the medial and intimal layers. The mean internal elastic lamina thickness was significantly higher in arteries from cases with isolated medial hypertrophy when compared with controls and to those with proliferative lesions (P <.05). The number of gaps of the internal elastic lamina was higher in arteries >100 micro m in diameter from the group with intimal lesions when compared to the cases presenting with isolated hypertrophy, but did not differ from the controls. There was a positive linear correlation between the external arterial diameter and the thickness of the internal elastic lamina (r =.74, P <.001) in cases presenting isolated medial hypertrophy. The increased thickness and smaller number of gaps of the internal elastic lamina may act as a barrier that prevents smooth muscle cell migration in patients with pulmonary hypertension without intimal proliferative lesions. On the other hand, a greater number of gaps does not represent, by itself, unrestrained migration, because controls also showed fenestrated laminae.
Biopsy↗
Elastic fiber production in cardiovascular tissue-equivalents.
Elastic fiber incorporation is critical to the success of tissue-engineered arteries and heart valves. Elastic fibers have not yet been observed in tissue-engineered replacements fabricated in vitro with smooth muscle cells. Here, rat smooth muscle cells (SMC) or human dermal fibroblasts (HDF) remodeled collagen or fibrin gels for 4 weeks as the basis for a completely biological cardiovascular tissue replacement. Immunolabeling, alkaline extraction and amino acid analysis identified and quantified elastin. Organized elastic fibers formed when neonatal SMC were cultured in fibrin gel. Fibrillin-1 deposition occurred but elastin was detected in regions without fibrillin-1, indicating that a microfibril template is not required for elastic fiber formation within fibrin. Collagen did not support substantial elastogenesis by SMC. The quantity of crosslinked elastic fibers was enhanced by treatment with TGF-beta1 and insulin, concomitant with increased collagen production. These additives overcame ascorbate's inhibition of elastogenesis in fibrin. The elastic fibers that formed in fibrin treated with TGF-beta1 and insulin contained crosslinks, as evidenced by the presence of desmosine and an altered elastin labeling pattern when beta-aminopropionitrile (BAPN) was added. These findings indicate that in vitro elastogenesis can be achieved in tissue engineering applications, and they suggest a physiologically relevant model system for the study of three-dimensional elastic structures.
Amino Acids↗
Time course of respiratory mechanics and pulmonary structural remodelling in acute lung injury.
The aim of this study was to evaluate the time course of in vivo and in vitro respiratory mechanics and examine whether these parameters could reflect the temporal changes in lung parenchyma remodelling in paraquat (PQ)-induced lung injury. Measurements were done 1, 3 and 8 weeks after the intraperitoneal (i.p.) injection of saline (control) or paraquat (7mgkg(-1)) in rats. Airway and tissue resistances increased from control in PQ1 and PQ3 and returned to control values in PQ8, in accordance with the magnitude of bronchoconstriction. Viscoelastic/inhomogeneous pressure, tissue elastance, the number of polymorphonuclear cells, and collagen fibre content in lung parenchyma increased in PQ1 and remained elevated in PQ3 and PQ8. Static elastance increased in PQ1, returned to control values after 3 weeks, and was correlated with the volume fraction of collapsed alveoli. In conclusion, there is a restoration of normal alveolar-capillary lung units with a gradual improvement in airway and tissue resistances and static elastance. However, the on-going fibrotic process kept elevated tissue elastance and viscoelastic/inhomogeneous pressure.
Airway Resistance↗
Dermal changes in osteoporosis following prolonged treatment with human growth hormone.
Five patients with osteoporosis were treated with human growth hormone (hGH) for a year and the changes in their skin were studied by light and electron microscopy. The abnormally thin skin of osteoporosis appeared to change towards normal after treatment with hGH. There was a consistent proliferation of blood vessels, and increased number of mast cells and fibrocytes. The collagen bundles and elastic tissue fibers appeared hyperplastic and more horizontally oriented. The fine, vertical elastic fibrils of the papillary dermis had appeared decreased before treatment, but seemed to be restored to their normal configuration after treatment. Since there was no evidence of stimulation of hair, sebum, or melanin such as occurs in acromegaly, it is suggested that the scope of the direct action of hGH on the skin is limited to mesenchymal structures.
Aged↗
A combined elastic, fibrin and collagen stain.
A method is described which demonstrates nuclei, elastic fibers, red blood cells, collagen and fibrin. Nuclei and elastic fibers are stained by a modified Verhoeff's elastic tissue stain which was previously developed and used in the elastic-Masson combination. Both early fibrin and red blood cells are shown by lissamine fast yellow. Mature fibrin, some types of collagen and other cytoplasmic changes are stained by a combination of acid fuchsin, Biebrich scarlet and ponceau 2R, while old fibrin is demonstrated by the collagen stain. This method takes about 1 hr to perform and has the added advantage that several entities are clearly shown in a single slide.
Cell Nucleus↗
Histologic and ultrastructural features of primary and secondary endocardial fibroelastosis.
The average size of elastic fibers in thickened left ventricular endocardium was much larger in four patients with congenital endocardial fibroelastosis (EFE) than in six patients with acquired EFE (secondary to ischemic heart disease in two patients, to prosthetic cardiac valves in three, and to irradiation of the chest in one). Both components of normal elastic tissue (central, amorphous cores, and peripheral microfibrils) were present in endocardial elastic fibers of each patient. Ultrastructural identification of elastic fibers was greatly facilitated by staining with silver tetraphenylporphin sulfonate.
Adult↗
Targetting of the gene encoding fibrillin-1 recapitulates the vascular aspect of Marfan syndrome.
Aortic aneurysm and dissection account for about 2% of all deaths in industrialized countries; they are also components of several genetic diseases, including Marfan syndrome (MFS). The vascular phenotype of MFS results from mutations in fibrillin-1 (FBN1), the major constituent of extracellular microfibrils. Microfibrils, either associated with or devoid of elastin, give rise to a variety of extracellular networks in elastic and non-elastic tissues. It is believed that microfibrils regulate elastic fibre formation by guiding tropo-elastin deposition during embryogenesis and early post-natal life. Hence, vascular disease in MFS is thought to result when FBN1 mutations preclude elastic fibre maturation by disrupting microfibrillar assembly. Here we report a gene-targetting experiment in mice that indicates that fibrillin-1 microfibrils are predominantly engaged in tissue homeostasis rather than elastic matrix assembly. This finding, in turn, suggests that aortic dilation is due primarily to the failure by the microfibrillar array of the adventitia to sustain physiological haemodynamic stress, and that disruption of the elastic network of the media is a secondary event.
Aortic Dissection↗
A new type of connective tissue nevus: isolated exophytic elastoma.
An unusual case of isolated exophytic elastic tissue nevi in the scrotal region of a 64-year-old man is described. The histological and ultrastructural findings were those of abundant abnormal elastic fibers and increased reticulin in the dermis. This hamartomatous lesion possesses clinical and histological features previously undescribed in connective tissue nevi.
Elastic Tissue↗