Tenascin-X: Clinical and Biological Aspects.

Contains fulltext : mmubn000001_43296407x.pdf (publisher's version ) (Closed access)KUN Katholieke Universiteit Nijmegen, 4 februari 2005Promotor : Schalkwijk, J. Co-promotor : Heijer, M. den144 p

Joint hypermobility syndromes: the pathophysiologic role of tenascin-X gene defects.

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DESA1002 'Continuous City' <Amy Tahere>

‘The curve’ is a space designed for relaxation, leisure, social gatherings, recreation and reconnection. It consists of a series of curved pathways, water gardens, a café, restaurant, bar, exhibition studio, a quiet hub, a gym and a heated pool. I have given my design the title ‘The curve’ not only for the visual form we can see, but also to represent my design intention. A ‘curve’ is defined as a line that deviates from straightness in a smooth, continuous fashion. It is part of a circle… Just as the term is described, my design is a space for people to deviate from routine life and confinement, and venture into a space where they feel comfortable and content; doing things they want to do. ‘The Curve’ provides a space where the citizens of Stockholm can find a healthy balance between work, family, friends and even reconnection with themselves. It helps complete the circle. ‘The Curve’ comes in contact with the main land in four places, leaving the existing building untouched. The curvaceous structure is influenced by the organic nature of Stockholm, a city that is renowned for its clean water and being one of the most green cities in Europe. ‘The curves’ varying heights reflect the topography of Stockholm’s Architecture, however on my site it contrasts with the parliament house which is very bold and solid. This is to represent the more relaxed and informal setting of the space. In Stockholm, for parts of the year they have less daylight, and to make my project appropriate for this, all areas are provided with solar lighting. Solar energy is stored from the summer months and is used over winter. Circulation paths will be highly illuminated. The main materials used are, double glazed glass cladding, galvanised steel and very fine grain timber piles for in the water, timber decking and grass cover. Where the paths connect with the main land there is a graduation of cobble stone which then transforms into a panel pathway that has round/ stone shaped illuminators beneath it. This pathways links Gamla Stan (The old City-Cobble stones) with the new (technology and illuminated panels).The choice of glass is to take full advantage of the water front location, the galvanised steel is for strength, long span and to be able to create the desired shape. Timber sliding panels have been implemented for the occupants to shade/shield certain areas to suit there needs. ‘The Curve’ has been an exciting and challenging project to focus on a single architectural built form within the restraints and opportunities of a complex urban setting

Abdominal aortic aneurysm is associated with high serum levels of tenascin-X and decreased aneurysmal tissue tenascin-X.

Contains fulltext : 50368schalkwijk.pdf (publisher's version ) (Closed access)BACKGROUND: Tenascin-X is a large extracellular matrix protein that is abundantly expressed in several connective tissues. A 140-kDa C-terminal fragment of tenascin-X is present in human serum. Complete deficiency of tenascin-X is associated with Ehlers-Danlos syndrome, and these patients show major connective tissue alterations in their skin, as well as blood vessel fragility. In this study, we investigated whether tenascin-X is present in normal human aorta and abdominal aortic aneurysm (AAA) tissues and whether an association exists between serum tenascin-X levels and AAA. METHODS AND RESULTS: Five normal aortas and 5 AAA tissues were immunostained for tenascin-X and elastin. Tenascin-X was present throughout the entire aorta and was especially abundant near the elastic lamellae, whereas tenascin-X expression was strongly decreased in AAA tissue. Measurement of tenascin-X serum concentration by enzyme-linked immunosorbent assay (ELISA) in 87 AAA patients and 86 controls demonstrated an increasing risk for AAA with increasing tenascin-X serum concentrations. After adjustment for established risk factors, tenascin-X serum concentrations in the highest quartile were associated with a 5-fold increase in risk of AAA (odds ratio, 5.3; 95% confidence interval, 2.0 to 13.8). CONCLUSIONS: Tenascin-X expression is markedly decreased in AAA tissue, and AAA is associated with high serum concentrations of tenascin-X

Dermal connective tissue development in mice: an essential role for tenascin-X.

Contains fulltext : 49590schalkwijk.pdf (publisher's version ) (Closed access)Deficiency of the extracellular matrix protein tenascin-X (TNX) causes a recessive form of Ehlers-Danlos syndrome (EDS) characterized by hyperextensible skin and hypermobile joints. It is not known whether the observed alterations of dermal collagen fibrils and elastic fibers in these patients are caused by disturbed assembly and deposition or by altered stability and turnover. We used biophysical measurements and immunofluorescence to study connective tissue properties in TNX knockout and wild-type mice. We found that TNX knockout mice, even at a young age, have greatly disturbed biomechanical properties of the skin. No joint abnormalities were noted at any age. The spatio-temporal expression of TNX during normal mouse skin development, during embryonic days 13-19 (E13-E19), was distinct from tropoelastin and the dermal fibrillar collagens type I, III, and V. Our data show that TNX is not involved in the earliest phase (E10-E14) of the deposition of collagen fibrils and elastic fibers during fetal development. From E15 to E19, TNX starts partially to colocalize with the dermal collagens and elastin, and in adult mice, TNX is present in the entire dermis. In adult TNX knockout mice, we observed an apparent increase of elastin. We conclude that TNX knockout mice only partially recapitulate the phenotype of TNX-deficient EDS patients, and that TNX could potentially be involved in maturation and/or maintenance of the dermal collagen and elastin network

Haploinsufficiency of TNXB is associated with hypermobility type of Ehlers-Danlos syndrome.

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A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency.

BACKGROUND: The Ehlers-Danlos syndrome is a heritable connective-tissue disorder caused by defects in fibrillar-collagen metabolism. Mutations in the type V collagen genes account for up to 50 percent of cases of classic Ehlers-Danlos syndrome, but many other cases are unexplained. We investigated whether the deficiency of the tenascins, extracellular-matrix proteins that are highly expressed in connective tissues, was associated with the Ehlers-Danlos syndrome. METHODS: We screened serum samples from 151 patients with the classic, hypermobility, or vascular types of the Ehlers-Danlos syndrome; 75 patients with psoriasis; 93 patients with rheumatoid arthritis; and 21 healthy persons for the presence of tenascin-X and tenascin-C by enzyme-linked immunosorbent assay. We examined the expression of tenascins and type V collagen in skin by immunohistochemical methods and sequenced the tenascin-X gene. RESULTS: Tenascin-X was present in serum from all normal subjects, all patients with psoriasis, all patients with rheumatoid arthritis, and 146 of 151 patients with the Ehlers-Danlos syndrome. Tenascin-X was absent from the serum of the 5 remaining patients with Ehlers-Danlos syndrome, who were unrelated. Tenascin-X deficiency was confirmed in these patients by analysis of skin fibroblasts and by immunostaining of skin. The expression of tenascin-C and type V collagen was normal in these patients. All five of these patients had hypermobile joints, hyperelastic skin, and easy bruising, without atrophic scarring. Tenascin-X mutations were identified in all tenascin-X-deficient patients; one patient had a homozygous tenascin-X gene deletion, one was heterozygous for the deletion, and three others had homozygous truncating point mutations, confirming a causative role for tenascin-X and a recessive pattern of inheritance. CONCLUSIONS: Tenascin-X deficiency causes a clinically distinct, recessive form of the Ehlers-Danlos syndrome. This finding indicates that factors other than the collagens or collagen-processing enzymes can cause the syndrome and suggests a central role for tenascin-X in maintaining the integrity of collagenous matrix