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Repair in arterial tissue. 2. Connective tissue changes following an embolectomy catheter lesion. The importance of the endothelial cells to repair and regeneration.

The neointimal hyperplasia following a severe mechanical lesion of the rabbit thoracic aorta was studied by vital staining with Evans blue and transmission electron microscopy. Neointimal tissue covered with endothelium contained organized laminated elastin-rich commective tissue. On the contrary neointimal connective tissue covered with pseudoendothelium was disorganized, with a tendency to fibrosis. Reendothelialization, re-establishment of intimal barrier function and formation of lamellated neointimal connective were parallel events. The importance of a intact subendothelial zone controlling healing processes is discussed. Interaction of endothelium and smooth muscle cells seems to be essential in the regulation of neointimal tissue formation and is probably implicated in a general vascular reactive pattern.

Animals

Free serum ribonucleoprotein in mixed connective tissue disease and other connective tissue diseases.

Free ribonucleoprotein (RNP) was found by means of a hemagglutination inhibition assay in 21 sera from 11 of 25 patients with mixed connective tissue disease (MCTD) who had 299 sera studied. Free RNP tended to appear when anti-RNP antibody titers fell or when prednisone was initiated or increased. Five of 72 SLE patients (211 sera) had free RNP in at least one serum. Three of them had anti-RNP antibodies in other sera. Free serum RNP was found in one of 20 patients with scleroderma and in two of seven patients with connective tissue disease "overlap" syndromes without anti-RNP.

Antibodies, Antinuclear

[Connective tissue polypeptides in serum: new parameters of connective tissue synthesis and degradation in liver fibrosis].

With the invention of drugs that effectively and specifically inhibit excessive collagen synthesis in the liver, a growing interest in serum assays that assess fibrogenesis, i.e. the de novo formation and fibrolysis, i.e. the removal of connective tissue in the liver, may be anticipated. Several serum assays for connective tissue polypeptides fulfil the criteria of sensitivity and specificity for chronic liver diseases. The aminoterminal procollagen type III peptide (PIIINP) correlates with hepatic fibrogenesis, whereas the propeptides of basement membrane collagen (PIVNP and PIVCP) and the basement membrane glycoprotein laminin reflect the enhanced turnover of basement membranes of the sinusoids as well as of proliferating bile ducts and blood vessels in active fibrosis. Circulating collagen type VI results from degradation of interstitial microfilaments and undulin appears to be released upon remodeling of the hepatic architecture. Combined measurement of selected parameters may allow a non-invasive assessment of the balance between fibrogenesis and fibrolysis on a day-to-day basis, especially in the light of potential antifibrotic therapy.

Biopsy

Connective tissue activation. XIII. Stimulation of sulfated glycosaminoglycan synthesis in human connective tissue cells by peptide mediators from lymphocytes and platelets.

CTAP-I from lymphocytes and CTAP-III from platelets markedly stimulated 35SO4= incorporation into chondroitin 4/6 sulfate and dermatan sulfate synthesized by human synovial, dermal, and cartilage connective tissue cells in vitro. These agonists promoted synthesis of the GAG carbon chain as well as sulfate incorporation. Both RNA and protein synthesis were required for these mediators to be effective in stimulating synthesis of connective tissue matrix components. A major part of the capacity of normal serum to stimulate sulfate incorporation into GAG's may reside in CTAP-III.

Blood Platelets

Oxygen and the connective tissues.

Avascular connective tissues (cartilage, discs, cornea) change with maturation and aging, particularly in large animals, where diffusion paths are longest. It is suggested that the changes in such tissues are responses to increasing difficulties in obtaining oxygen. Two almost identical structural polymers are made in these tissues: chondroitin sulphate, which requires large amounts of oxygen for biosynthesis and keratan sulphate, which requires relatively little. The observed balance of these polymers in the tissue is proposed to depend on the control of biosynthesis by the ambient oxygen tension, and/or selective breakdown.

Animals

Immunofluorescence studies with a specific antiserum to the microfibrillar protein of elastic fibres. Location in elastic and non-elastic connective tissues.

The microfibrillar protein (MFP) of foetal bovine ligamentum nuchae elastic fibres was prepared and used to produce a monospecific antiserum. Indirect immunofluorescence studies employing the specific antiserum demonstrated its selectivity for MFP associated with elastic fibres. The antiserum was demonstrated to react with vascular elastic tissue, perivascular connective tissue and reticular basement membranes in a variety of tissues. This evidence suggests that the MFP (or an immunologically related protein) is not confined to elastic fibres but is widely distributed in connective tissue being associated with both elastin and collagen fibres.

Animals

Gastrointestinal systemic sclerosis in serologic mixed connective tissue disease.

Mixed connective tissue disease is a clinical entity defined by overlapping features of progressive systemic sclerosis, systemic lupus erythematosus, polymyositis, rheumatoid arthritis, and distinct serologic findings. Esophageal dilatation and dysmotility have been the only gastrointestinal manifestations reported. Three patients with serologic findings of mixed connective tissue disease and extensive gastrointestinal involvement compatible with the changes found in progressive systemic sclerosis are presented. Gastrointestinal manifestations of progressive systemic sclerosis are reviewed and were found to be indistinguishable from the findings in these patients.

Adult

Development of a polyepoxy compound cross-linked heterologous connective tissue tube.

A heterologous connective tissue tube with "built-in" polyester mesh was developed using a rabbit subcutaneous tissue and polyepoxy compound cross-linking method. To evaluate the graft, 11 grafts were implanted end to end in the position of the thoracic aorta of 11 dogs and evaluated from 1 hr to 80 days after surgery. The graft was white and pliable, and the mesh was seen through the connective tissue. The handling characteristics were good, and no bleeding was observed from either the graft wall or suture holes. Macroscopically, at 1 hour, the luminal surface was covered with a thin thrombus layer. At 80 days, most of the inner surface of the explanted graft was white and shiny without irregularity, but a small area of blood stain was observed. Microscopically, fibroblasts were observed in the graft wall at 7 days; capillaries penetrating to the luminal surface appeared at 29 days. Bleeding was rarely observed around the fabric. A layer of donor connective tissue was still observed at 80 days. No foreign body reaction was observed except around the mesh. It was concluded that the graft healed well and could be an arterial substitute.

Animals

Pulmonary hypertension in a child with mixed connective tissue disease.

Mixed connective tissue disease (MCTD) is characterized by high titers of antibody to ribonucleoprotein (RNP) in patients with features of several rheumatic diseases. We describe a child whose MCTD included arthritis, Raynaud's phenomenon, mucocutaneous ulcerations, sclerodermatous skin changes, restrictive lung disease, reduced carbon monoxide pulmonary diffusing capacity, abnormal esophogeal motility, and severe pulmonary hypertension. High antibody titers to ds-DNA and RNP were present. Clinical improvement followed therapy with prednisone and cyclophosphamide. Improvement in the degree of pulmonary hypertension was documented by repeat cardiac catheterization 8 months after the initiation of combination therapy.

Adolescent

[New results on ageing of connective tissue (author's transl)].

Some new results on ageing of connective tissue are demonstrated, regarding not only mesenchymal, but also parenchymal organs of human and rat (both sexes). These results show that ageing of connective tissue is more a dynamic process (with measurable metabolic parameters of the several connective tissue cells and their products) than a passive or so-called degenerative connective tissue process. The bradytrophy concept of connective tissue cannot be accepted any longer. Then connective tissue cells can produce metabolic rates of the same level like parenchymal cells. The different organs possess partly common basic processes partly differences in connective tissue ageing, dependent on the composition and patterns of proteoglycans resp. of GAG and collagen types, furthermore dependent on localisation, structure and function. The results on ageing of connective tissue are useful for better understanding of ageing processes of parenchymal organs. Then their ageing is influenced essentially by the ageing of the own connective tissues. The turnover, more than the number of mesenchymal and parenchymal cells, decreases with ageing. More old than young cells seem to exist in old tissues and organs. The performance of ageing connective tissue cells can be constant or increase or decrease. Many mesenchymal and parenchymal organs develop a so-called "ageing-fibrosis".

Aged

Overlapping syndromes, undifferentiated connective tissue disease, and other fibrosing conditions.

Many patients presenting with symptoms suggestive of a connective tissue disease do not fulfill criteria for a specific connective tissue disease at initial presentation. Some of these patients with undifferentiated connective tissue disease eventually develop a specific connective tissue disease. Recently, a large cohort of 213 patients from different centers with undifferentiated connective tissue disease of early onset were enrolled in a prospective protocoled study. Baseline characteristics, including antinuclear antibody profiles, were reported. The aim of this study was to define predictors for the development of specific organ-system involvement and connective tissue diseases in early undifferentiated connective tissue disease. Many patients show overlapping features of two or more connective tissue diseases. The presence of autoantibodies to U1-ribonucleoproteins has been associated with a particular overlap syndrome, mixed connective tissue disease. Most anti-U1-ribonucleoprotein-positive patients with undifferentiated connective tissue disease at presentation appear to develop mixed connective tissue disease over the course of disease. Although levels of anti-U1-ribonucleoprotein do not seem to be related to disease activity, this association suggests a pathogenetic relationship between anti-U1-ribonucleoprotein and mixed connective tissue disease. Genetic studies have shown that patients with antibodies against the 70-kD component of U1-ribonucleoprotein share a common epitope within the groove of their DR molecules at antigen-binding region, pointing to a particular antigen involved in the induction of these antibodies that may be relevant in the etiopathogenesis of associated disease.

Antibodies, Antinuclear

The hand in mixed connective tissue disease.

The mixed connective tissue disease syndrome has been described in the medical literature. The clinical and serological characteristics of the syndrome are defined in this paper. The hands of these patients differ from the hands of patients with systemic lupus, rheumatoid arthritis, or systemic sclerosis. In 10 patients there were no erosive changes on radiological examination and all 10 patients had Raynaud's phenomenon. The most striking finding was tightness in the flexors. Mild cases of flexor tightness improved with systemic steroids. One patient with severe flexor tightness required surgical release of adhesions from a chronic inflammatory process of fascia, muscle, and tenosynovium. Biochemical studies showed an abnormal collagen pattern that may be distinct for mixed connective tissue disease.

Adolescent