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Granuloma annulare: an elastic tissue disease? Case report and literature review.

Granuloma annulare (GA) is a condition characterized by the presence of palisading granulomas usually in the dermis. Traditionally, the histopathological changes are described as consisting of focal degeneration of dermal collagen fibers. However, no convincing evidence for such alteration is found in the literature. A histopathological study was done to ascertain the nature of the dermal abnormality. Ten skin biopsies showing lesions of GA were studied by light and electron microscopy. On light microscopy, all lesions showed focal dermal degeneration with near total loss of elastic fibers. Ultrastructural examination in nine cases demonstrated degenerated elastic fibers with loss of peripheral microfibrils and abnormal elastic matrix. The degenerated elastic fibers were surrounded by intact collagen fibers. These findings show that the main alteration in GA is elastic fiber degeneration and strongly suggest that the primary target leading to the development of this disorder is injury to the elastic tissue.

Adult↗

Post-embedding methods for immunolocalization of elastin and related components in tissues.

Elastic tissue is composed of amorphous-appearing elastin and 12-nm diameter microfibrils, one component of which has recently been isolated and characterized as the 31 KD microfibril-associated glycoprotein MAGP. Monospecific antibodies to each of these components have been developed in this laboratory. The parameters that determine optimal localization of colloidal gold probes for post-embedding immunolabeling of elastic tissue components have been systematically studied in a variety of normal and developing tissues in mammals and birds. Protein A-gold probes stabilized with dextran have been shown to provide complexes that remain stable after more than 2 years. Conditions have been defined that permit precise localization within the extracellular matrix of antibodies to MAGP and to elastin, singly and together. Best results were obtained with acrylic resins (Lowicryl K4M or LR White). Fixation in glutaraldehyde or other aldehydic fixatives, with or without osmium, did not affect the immunostaining of elastic tissue with affinity-purified antibodies to tropoelastin, or to anti-[alpha-elastin] or anti-[alkali-insoluble elastin]. Immunostaining with the anti-MAGP antibody was less robust and was possible in tissues which had been fixed only lightly before embedding in Lowicryl K4M or LR White. This staining was enhanced by metaperiodate oxidation of the sections as well as by reduction of the tissues with sodium borohydride en bloc, followed by hyaluronidase digestion of the sections. The effects on immunostaining of a range of enzyme digestions have also been examined. Conditions have thus been defined that make possible detailed study of the relationship between elastic tissue, elastin-associated microfibrils, and other microfibrillar structures in normal and abnormal tissues during development and aging.

Animals↗

Brain tissue elastic behavior and experimental brain compression.

This study was designed to test the hypothesis that the progressive expansion of an extradural mass causes detectable changes in brain mechanical response properties, in particular the nonlinear elastic behavior, before any significant changes in intracranial cerebrospinal fluid pressure can be detected. In 10 chronically prepared and anesthetized dogs, incremental inflation (0.07 ml/s) of an extradural balloon caused 1) a progressive fall in the brain nonlinear elastic parameter (G0, mmHg/mm2), 2) nonsignificant changes in brain tissue elasticity (G0, mmHg/mm), 3) a disproportionate progressive rise in subpial tension, and 4) a progressive fall in local cerebral blood flow (H2 clearance), despite a modest decrease in cerebral perfusion pressure (extracranial). In previous brain compression experiments (Brain Res. 305: 141-143, 1984) we have shown that the compression site becomes compacted and stiffer (increased G0) and its nonlinear elastic parameter (G0) increases markedly. These earlier findings, coupled with the present observation of a loss in tissue nonlinearity distally to the compression site, are most likely the major mechanisms by which, with a rapidly expanding intracranial mass, tissue pressure gradients and brain displacement, including transtentorial herniation, develop.

Animals↗

Microfibrillar protein from elastic tissue: a critical evaluation.

Many workers have claimed to have isolated proteins which have been derived from the microfibrillar components of elastic tissue. Virtually all of these preparations have been derived from extracts made with strong solutions of guanidinium chloride (GuHCl) under reducing conditions following Ross and Bornstein (1969). The products have ranged from heterogeneous mixtures of proteins to discrete glycoproteins. In no case has identity between an individual protein and the elastin-associated microfibrils been confirmed by immunoelectron microscopy. We have undertaken a detailed re-examination of the extractability of elastin-associated microfibrils and of the composition of the extracts from foetal bovine nuchal ligament. Finely homogenized samples were subjected to a series of extractions (including cyclical treatments with GuHCl and purified bacterial collagenase) in the presence of inhibitors of protease activity. Under these conditions it has been shown that--(i) microfibrils were removed progressively by GuHCl, throughout the extraction schedule, without the need for reduction; (ii) all remaining microfibrils were removed by reductive GuHCl extraction; (iii) the product from this reductive extraction consisted of a heterogeneous mixture of proteins including several glycoproteins; (iv) a major antigenic constituent of the mixture of proteins localized to elastin-associated microfibrils, as shown by immunoelectron microscopy. It is concluded that, while reductive GuHCl extracts do contain components with antigenic activity that is localized on elastin-associated microfibrils, they have many non-microfibrillar components. We stress that claims that a macromolecule is microfibrillar must be substantiated by immunoelectron microscopy.

Animals↗

Destruction of elastic tissue (elastolysis) as a link between atherosclerosis and the temporal arteritis/polymyalgia rheumatica syndrome. Observations on an actinic factor in vascular disease.

Destruction (elastolysis) of the internal elastic lamina is frequently observed near early atherosclerotic plaques. Elastolysis and plaque formation are also found together in the temporal arteritis/polymyalgia rheumatica syndrome. Could it be that atherosclerosis and the syndrome are more closely akin than usually thought, with elastolysis acting as the pathogenetic link between them? A kinship of this nature is in accord with the growing recognition that elastin-related autoimmunity prevails in both these forms of vascular disease. A case can also be made out for the belief that the autoimmune reactions in internal vessels may be provoked by events in the integument where a slow but ultimately massive turnover of dermal and vascular elastic tissue takes place under the harmful influence of solar and other forms of actinic radiation.

Arteriosclerosis↗

A distributed nonlinear model of lung tissue elasticity.

We present a theory relating the static stress-strain properties of lung tissue strips to the stress-bearing constituents, collagen and elastin. The fiber pair is modeled as a Hookean spring (elastin) in parallel with a nonlinear string element (collagen), which extends to a maximum stop length. Based on a series of fiber pairs, we develop both analytical and numerical models with distributed constituent properties that account for nonlinear tissue elasticity. The models were fit to measured stretched stress-strain curves of five uniaxially stretched tissue strips, each from a different dog lung. We found that the distributions of stop length and spring stiffness follow inverse power laws, and we hypothesize that this results from the complex fractal-like structure of the constituent fiber matrices in lung tissue. We applied the models to representative pressure-volume (PV) curves from patients with normal, emphysematous, and fibrotic lungs. The PV curves were fit to the equation V = A--Bexp(-KP), where V is volume, P is transpulmonary pressure, and A, B, and K are constants. Our models lead to a possible mechanistic explanation of the shape factor K in terms of the structural organization of collagen and elastin fibers.

Animals↗

[Three-dimensional observation of elastic tissue in Bruch's membrane by formic acid extraction].

Japanese monkey and albino rabbit choroid were treated with hot-formic acid to remove the cellular elements and the extracellular matrices excluding the elastic tissues so that both three-dimensional and bird's eye views of the elastic layer of Bruch's membrane could be obtained. The only elastic layer was extracted and observed with a scanning electron microscope. Elastic layers were frequently extracted as translucent monolayered sheets with oval, sector-shaped fenestrations of varying sizes. Elastic fibers of 100-200nm in diameter crossed each other in these fenestrations. Other fine fibers connecting these elastic fibers and their sheet-like elastic plate were also observed. In Japanese monkey eyes, lattice structures formed by thick elastic fibers, 200-300nm in diameter, were conspicuous. This method proved suitable for the observation of the three-dimensional structure of the elastic layer of Bruch's membrane.

Animals↗

Iron gallein elastic method---a substitute for Verhoeff's elastic tissue stain.

A method for staining elastic fibers in formalin fixed, paraffin embedded sections is described. After deparaffinizing and dehydration, sections are stained for 30 minutes in a solution prepared by mixing equal parts of 1% gallein dissolved in ethylene glycol and absolute alcohol (1:4), and 1.16% aqueous ferric chloride in 1% hydrochloric acid. The sections are washed in water and then differentiated in 2% ferric chloride for 2 minutes. After washing in water, the sections are counterstained with a variant of Van Gieson's picric acid-acid fuchsin for 1 minute. The results are similar to Verhoeff's elastic stain with elastic fibers staining black. An advantage to this staining procedure is that visually controlled differentiation is not necessary.

Aorta↗

Changes in the elastic tissue of the non-sun-exposed skin of cigarette smokers.

Biopsies were taken from the upper and inner arm of 10 60-year-old male cigarette smokers and compared with 10 age-matched controls who were non-smokers. The mean relative area, number and thickness of the elastic fibres were significantly increased in the cigarette smokers compared to the controls. These results were confirmed using antibodies to elastin or the microfibrillar component of elastic tissue. In the smokers the broader and more fragmented elastic fibres in the skin were not as intensely stained as those of the non-smokers and the ultrastructural alterations of the elastic fibres were similar to those in solar elastosis.

Antibodies↗