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Connective tissues: signalling by tenascins.

Different connective tissue cells secrete different types of tenascins. These glycoproteins contribute to extracellular matrix (ECM) structure and influence the physiology of the cells in contact with the tenascin containing environment. Tenascin-C expression is regulated by mechanical stress. It shows highest expression in connective tissue surrounding tumors, in wounds and in inflamed tissues where it may regulate cell morphology, growth, and migration by activating diverse intracellular signalling pathways. Thus, integrin and syndecan signalling is influenced by tenascin-C and the levels and/or activies of several proteins involved in intracellular signalling pathways are regulated by its presence. Tenascin-X is important for the proper deposition of collagen fibers in dermis and patients with a tenascin-X deficiency suffer from Ehlers Danlos syndrome. Tenascin-R (and -C) is prominent in the nervous system and has an impact on neurite outgrowth and synaptic functions, and tenascin-W is found in the extracellular matrix of bone, muscle, and kidney. Cell facts:bone: osteoblasts produce tenascin-C, -W cartilage: perichondrial cells produce tenascin-C tendon: fibroblasts produce tenascin-C smooth muscle cells produce tenascin-W, -C skeletal muscle: endo-, peri-, and epimysial fibroblasts produce tenascin-X dermal fibroblasts produce tenascin-X tumors: stromal fibroblasts produce tenascin-C wounds: fibroblasts produce tenascin-C nervous system: glial cells produce tenascin-R, -C, -X.

Cell Shape↗

Gingival recession treatment: guided tissue regeneration with bioabsorbable membrane versus connective tissue graft.

BACKGROUND: Gingival recession represents a significant concern for patients and a therapeutic problem for clinicians. Several techniques have been proposed to achieve root coverage. The purpose of this randomized clinical trial was to evaluate the effect of a guided tissue regeneration (GTR) procedure in comparison to connective tissue graft (CTG) in the treatment of gingival recession defects. METHODS: Twelve patients, each contributing a pair of Miller Class I or II buccal gingival recessions, were treated. In each patient one randomly chosen defect received a poly(lactic acid)-based bioabsorbable membrane, while the paired defect received a CTG. Clinical recordings included oral hygiene standards and gingival health, recession depth (RD), recession width (RW), probing depth (PD), clinical attachment level (CAL), and keratinized tissue width (KT). RESULTS: Mean RD statistically significantly decreased from 2.5 mm presurgery to 0.5 mm with GTR (81% root coverage), and from 2.5 mm to 0.1 mm with CTG (96% root coverage), at 6 months postsurgery. Prevalence of complete root coverage was 58% for the GTR group and 83% for the CTG group. Mean CAL gain was 2.0 mm for the GTR group and 2.2 mm for the CTG group. No statistically significant differences between treatment groups were observed for changes in RD, RW, PD, CAL, and KT. CONCLUSIONS: Treatment of human gingival recession defects by means of either GTR or CTG results in clinically and statistically significant improvement of the soft tissue conditions of the defect when pre- and post-treatment measurements were compared. Although differences between CTG and GTR in mean root coverage and prevalence of complete coverage consistently favored the CTG procedure, the differences in measurements were not statistically significant.

Absorbable Implants↗

Failure to detect paramyxovirus RNA in the skin of connective tissue disease.

Etiology of connective tissue disease is unknown. The association of infectious agents has been suspected serologically, ultrastructurally and recently by means of molecular biological techniques. We extracted RNA from lesions of 25 discoid lupus erythematosus, 9 systemic LE, and 3 systemic sclerosis biopsies, and reverse transcription-polymerase chain reaction was performed for all paramyxoviruses known to infect human beings. None of the samples yielded positive signal for any of the viruses. The existence of paramyxovirus in the skin of connective tissue disease is very unlikely.

Base Sequence↗

Determination of subepithelial connective tissue graft thickness in the dog.

PURPOSE: In this study, we determined the tissue thickness of healed subepithelial connective tissue grafts, the type of tissue present after healing, and the percentage of shrinkage of subepithelial connective tissue grafts over time in the facial aspect of the canine maxilla. MATERIALS AND METHODS: Four dogs each received 2 single-thickness subepithelial connective tissue grafts, 2 double-thickness grafts, and 2 sham-operated sites in the facial aspect of the maxilla bilaterally. The subepithelial connective tissue graft was harvested from the palate and included the periosteum. After the creation of a pouch on the facial aspect of the maxilla, the grafts were sutured directly to the maxillary periosteum and additional sutures were placed to secure the overlying mucosal flap to the graft. Thickness measures of the grafts before placement and after surgery with the grafts in place were made biweekly with a calibrated probe using known reference points on the teeth. Thickness measures were analyzed using a random-effects mixed model. All dogs were killed at 12 weeks, and the tissues were fixed, serially sectioned, and stained with hematoxylin and eosin for microscopic examination. RESULTS: Initial measurements of the sites demonstrated a thickness of 1.5 +/- 0.6 mm. Immediate postoperative measures were 7.1 mm (single thickness), 7.0 mm (double thickness), and 4.8 mm (sham operated). Week 6 measures were 3.9 mm (single thickness), 3.6 mm (double thickness), and 2.7 mm (sham operated), and week 12 measures were 3.9 mm (single thickness), 3.4 mm (double thickness), and 2.9 mm (sham operated). The difference between single- and double-thickness grafts was not significant (P =.34). The differences between single thickness and sham operated (P =.0036) and between double thickness and sham operated (P =.0049) were significant. Microscopic evaluation demonstrated that the grafts were indistinguishable from the adjacent subcutaneous tissues of the maxilla. The submucosal graft region contained fat, small blood vessels, nerves, and fibrous connective tissue. CONCLUSIONS: Based on this study in dogs, shrinkage of subepithelial grafts can be expected. The grafts become incorporate into the host tissues and appear similar to the normal connective tissue.

Analysis of Variance↗

A neoplastic connective tissue mast cell capable of continuous growth in tissue culture.

A neoplastic connective tissue mast cell from a dog mast cell sarcoma has been grown in tissue culture for 50 passages over a period of 2 years. The cells were grown as monolayer cultures in glass bottles, using Eagle's basal medium fortified with calf serum. The cultures were contaminated with an Alkaligenes sp. for 10 months but finally were sterilized bacteriologically by treatment with specific antiserum combined with antibiotics. The cells grow in a fibroblastic pattern, and contain mitochondria, mast cell granules, and lipid granules or droplets. The mast cell granules stain basophilic with Giemsa's stain and metachromatically with azure A or toluidine blue. They also stain with Sudan black B and with periodic acid-Schiff stain. The interphase nuclei are vesicular, contain from 1 to 20 nucleoli, and frequently show bizarre outlines. Multinucleate cells are often seen, as are mitotic figures. Extracellular fibrous material occurs in all cultures and apparently originates from the cell surface. This material does not have the structure of connective tissue fibers and has not been identified. The cells develop an increased number of metachromatic granules when grown in medium containing heparin and an increased number of sudanophilic granules when grown in medium containing stearic acid. Only small amounts of histamine were present in the tumor from which this cell line was derived and in the cells grown in tissue culture.

Animals↗

Connective tissue activation. XXII. A platelet growth factor (connective tissue-activating peptide-III) in human growth hormone-deficient patients.

Connective tissue-activating peptides (CTAPs) stimulate human synovial cells to exhibit a higher rate of DNA synthesis, glycolysis, and glycosaminoglycan formation. These bioactive peptides have been isolated from human platelets (CTAP-III), lymphocytes, tumor cells, and neutrophilic leukocytes. Several other growth factors, such as somatomedins A and C and nonsuppressible insulin-like activity (soluble), have been shown to be dependent on the circulating levels of pituitary GH. In this study, we examined the human GH (hGH) dependence of CTAP-III. Platelets from children with reduced or absent hGH were examined for the presence of CTAP-III. The peptide was detected qualitatively by polyacrylamide gel electrophoresis and Ouchterlony double diffusion. CTAP-III antigen, measured by RIA, was found in normal amounts in platelet lysates from normal persons and GH-deficient patients. Biological activity of the peptide was suggested by the ability of platelet lysates to stimulate the formation of glycosaminoglycans and increase sulfate incorporation into glycosaminoglycans formed in cell cultures. In addition, normal and hGH-deficient platelet lysates contained potent mitogenic activity which increased thymidine incorporation into DNA. Platelets from GH-deficient patients also released CTAP-III normally on exposure to thrombin.

Adolescent↗

[Second degree atrioventricular block in mixed connective tissue disease].

INTRODUCTION: Mixed connective tissue disease (MCTD) is characterized by overlapping features of progressive systemic sclerosis, dermatomyositis and systemic lupus erythematosus, and by high rate of antibodies to an extractable nuclear antigen ribonucleoprotein. Cardiac manifestations in MTCD are rare. EXEGESIS: A 58 years old man was admitted for mild fever, a impairment of the general status, muscular pain and a Raynaud's phenomenon. Biologic abnormalities were an inflammatory syndrome, elevated serum CPK and high rate anti-RNP antibodies. Diagnosis of mixed connective tissue disease was made. Shortly after, a Wenckebach atrioventricular block occurred. Systemic corticosteroids were efficient. CONCLUSION: Heart blocks are rarely described in MCTD. Three cases have been reported. It's a systemic complication resulting of an inflammatory process often responsive to steroids.

Connective Tissue Diseases↗

A comparison of 2 root coverage techniques: guided tissue regeneration with a bioabsorbable matrix style membrane versus a connective tissue graft combined with a coronally positioned pedicle graft without vertical incisions. results of a series of consecutive cases.

Root coverage procedures have become an important part of periodontal therapy. The purpose of this study was to compare 2 techniques, 1) guided tissue regeneration (GTR) with a bioabsorbable polylactic acid softened with citric acid ester membrane and 2) the connective tissue graft combined with a coronally positioned pedicle graft without vertical incisions. The GTR procedure produced a mean root coverage of 92.3% and the connective tissue graft combined with a coronally positioned pedicle graft, 95.0%. This difference was not statistically significant. Both procedures produced similar reductions in recession depth, recession width, and probing depth. The connective tissue graft combined with a coronally positioned pedicle graft resulted in a greater increase in the amount of keratinized tissue. Based on this study, both procedures can result in statistically similar amounts of mean root coverage, but the results are not identical. In most cases, the connective tissue with coronally positioned pedicle graft produced a more bulky result than guided tissue regeneration. Therefore, the procedures are not interchangeable.

Adult↗

Histochemistry of connective tissue cells in subcutaneous adipose tissue of normal and decapitated pig fetuses.

Connective tissue cells that are histochemically and morphologically distinct from 'fibroblasts' are localized around developing hair follicles in the pig and rat. Immature adipose tissue is limited to small areas immediately around fully descended hair follicles in the rat hypodermis. In the present study, connective tissue around large nerves and blood vessels in fetal pig subcutaneous tissue was examined for the presence of enzymes typical of adipocytes. Samples from decapitated pig fetuses were studied so that the effects of an altered hormonal profile could be examined. Samples of dorsal subcutaneous adipose tissue were obtained from fetuses at 65, 70, 85, 90, 110, and 112 days of gestation. Fetuses were decapitated in utero at 45 days of gestation, and adipose tissue samples were obtained from these fetuses at 110 days of gestation. A close spatial relationship was observed between the growth of large blood vessels and nerves and fat cell cluster development in the older (greater than 70 days) fetuses. Connective tissue cells that were contiguous with fat cell clusters were histochemically identical to adipocytes. The lipid histochemistry of the reactive connective tissue cells (histochemically identical to adipocytes) was variable in young fetuses. In all 110-and 112-day-old fetuses, the reactive cells contained lipid, whereas the reactive cells in decapitated fetuses were devoid of lipid. The reactive connective tissue cells were not associated with capillaries and did not contain basement membranes. The histochemistry of these cells suggests that they respond to a particular hormonal or metabolic profile as do adipocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Comparative clinical study of guided tissue regeneration with a bioabsorbable bilayer collagen membrane and subepithelial connective tissue graft.

BACKGROUND: During the last decade, there have been great strides in the treatment of gingival recession defects, especially with subepithelial connective tissue graft and guided tissue regeneration (GTR) procedures. Gingival recession represents a significant concern for patients. It is necessary to choose the most appropriate procedure in order to obtain more root coverage while avoiding clinical disadvantages. The purpose of this randomized clinical trial was to evaluate the use of a bioabsorbable bilayer collagen membrane with GTR compared to a connective tissue graft in the treatment of gingival recession defects. METHODS: Twenty patients each contributing a pair of Miller Class I or II buccal gingival recessions were treated. In each pair, one recession was randomly assigned for treatment with GTR using a bioabsorbable bilayer collagen membrane and the other treated with subepithelial connective tissue graft (CTG). Clinical measurements taken at baseline (D0) and 3 and 6 months post-treatment included recession depth (RD), recession width (RW), probing depth (PD), and clinical attachment level (CAL). RESULTS: Data were analyzed using the non-parametric Wilcoxon matched pair test. All results were statistically significant. Both treatments resulted in a significant gain of root coverage (P<0.0001), amounting to an average of 2.80 mm at 3 months in the GTR group and 3.34 mm in the CTG group. At 6 months, the decrease of the mean RD remained statistically significant: 2.70 mm (74.59% root coverage) in the GTR group and 3.19 mm (84.84% root coverage) in the CTG group. The mean RW also decreased from 4.48 mm at D0 to 2.42 mm at 6 months in the GTR group, and from 4.38 mm at D0 to 1.35 mm at 6 months in the CTG group, representing a percentage of coverage of 45.98% and 69.18%, respectively. Mean CAL gain obtained between D0 and 6 months with the GTR procedure and CTG was 3.31 mm and 3.09 mm, respectively, and was significant within groups. At 3 and 6 months, the differences in the results for RD, CAL, and RW were not statistically significant between the 2 groups. However, the difference was significant for PD at 3 and 6 months. CONCLUSIONS: The results suggest that a bioabsorbable bilayer collagen membrane can be used in the GTR treatment of human buccal recession defects, with no statistically significant differences between this procedure and connective tissue grafts.

Absorbable Implants↗

Connective tissue arrangement in respiratory airways.

Connective tissue provides dynamic stability to the architecture and mechanical function of the lungs. This study examines the parenchymal connective tissue components of the alveolar ducts, their associated respiratory bronchioles and respective alveoli. Thick sections 100 mu and 200 mu, and serial sections at 8 mu of lungs of different ages were examined histologically after fixation in distention. The varying proportions and spatial architecture of the collagen and elastic fibers and the packing and spatial interrelationships of alveoli were studied using graphic serial reconstruction. Alveolar mouth typically have a polygonal configuration as they arise from the airways. Denser connective tissue passes through the polygonal array and forms a helix encircling the airway. Polygonal packing of alveolar mouths provides a mechanically stable ductular structure with conservation of materials. A helical modification of the polygonal arrangement permits reversible changes in linear and circumferential airway dimensions.

Adult↗

Regulation of glucose transporters by connective tissue activating peptide-III isoforms.

Connective tissue activating peptide-III (CTAP-III) is a component of platelet alpha-granules which elicits a series of responses in connective tissue cells referred to as activation, including increased glucose consumption and mitogenesis and increased secretion of hyaluronic acid and glycosaminoglycans. As anticipated by a requirement for glucose or glucose precursors in the activation process, an early event following CTAP-III activation of connective tissue cells is an increase in glucose transport. The present study investigates the molecular basis for this increase in glucose transport. Murine 3T3-F442A fibroblasts were found to respond to CTAP-III in a manner similar to human connective tissue cells (synovial cells, chondrocytes, skin fibroblasts). CTAP-III increases the rate of glucose transport to similar extents at 4 and 24 h, and at physiologic (micrograms/ml) concentrations of CTAP-III. A proteolytic cleavage product of recombinant CTAP-III (rCTAP-III-Leu-21 (des-1-15)), also known as neutrophil-activating peptide-2 (NAP-2), was found to be equally effective as CTAP-III, whereas NAP-1/interleukin-8, another member of the CTAP-III super-family, was ineffective in stimulating glucose transport. This contrasts with neutrophil chemotaxis, in which CTAP-III (des-1-15)/NAP-2 acts similarly to NAP-1/interleukin 8 while CTAP-III is ineffective. CTAP-III appears to elicit a different type of glucose transport response than many other growth factors in that its response is sustained (greater than or equal to 24 h) rather than transient (peak approximately 4 h) in confluent as well as in subconfluent cells. Western blot analysis using antibodies to the GLUT-1 glucose transporter revealed an increased level of GLUT-1 protein in response to CTAP-III isoforms that corresponded in magnitude (on a percentage basis) to the increased level of glucose transport. The increased levels of GLUT-1 protein in response to CTAP-III and rCTAP-III-Leu-21 (des-1-15)/NAP-2 were accompanied by an increase in levels of GLUT-1 mRNA of a magnitude sufficient to account for observed increased levels of GLUT-1. These results are consistent with CTAP-III isoforms stimulating glucose transport in connective tissue cells by increasing levels of GLUT-1 mRNA and is one of the few known instances in which increases in levels of GLUT-1 mRNA and protein are sufficient to account for observed increases in glucose transport. They also provide further evidence that CTAP-III (des-1-15)/NAP-2 binds to more than one type of receptor and that CTAP-III acts in a manner different than other well characterized growth factors (e.g. platelet-derived growth factor, transforming growth factor-beta) in that it causes a sustained (greater than or equal to 24 h) elevation in glucose transport in confluent as well as subconfluent cells.

3T3 Cells↗

[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↗

Expression of connective tissue growth factor in intra-abdominal adhesions.

PURPOSE: Connective tissue growth factor stimulates fibroblast proliferation and extracellular matrix deposition in many fibrotic disorders. The aim of our study was to determine the expression pattern of connective tissue growth factor in postoperative intra-abdominal adhesions. METHODS: Adhesions were created in 46 Sprague-Dawley rats by complete dissection and resuturing of a peritoneal patch 2 cm in diameter, lateral from the midline incision. Animals were killed at postoperative Days 3, 6, 9, 12, 15, 18, and 21 and the adhesions scored on a scale of 0 to 5. Tissue samples from adhesion areas and from uninvolved peritoneum were evaluated by Northern and Western blotting for temporal connective tissue growth factor mRNA and protein expression, respectively. Immunohistochemical analysis was performed for connective tissue growth factor localization. RESULTS: Adhesions formed in all animals after surgery and were confined to the peritoneal patches. Adhesion formation increased across time, with significant correlation between adhesion scores and postoperative days (r = 0.329, P = 0.026). Connective tissue growth factor mRNA concentrations were significantly elevated in adhesion tissue throughout the three-week period when compared with normal peritoneum (P = 0.012); peak levels occurred between Days 6 and 15. Western blots demonstrated connective tissue growth factor protein expression in adhesions from Days 6 to 21, in contrast to negligible bands in normal peritoneum. Fibroblasts within the adhesive tissue, but not in uninjured peritoneum, stained positive for connective tissue growth factor by immunohistochemistry. CONCLUSIONS: We have demonstrated a specific temporal and spatial expression pattern for connective tissue growth factor in intra-abdominal adhesions during a three-week postoperative time course. According to what is known about the functional role of connective tissue growth factor in fibrogenesis, our findings warrant further investigations addressing a causal relationship between this growth factor and fibrous adhesion formation.

Animals↗

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↗

Protein-losing enteropathy and pancreatic involvement in a case of connective tissue disease.

A patient with connective tissue disease presenting with both protein-losing enteropathy and pancreatic involvement is reported. A 52-year-old female was admitted because of mild epigastralgia, anasarca and ascites. Serum albumin, transferrin and zinc, showed low levels. An Upper G.I. series and endoscopy showed thickened folds of the duodenum and the jejunum. Biopsy specimens revealed lymphangiectasia in edematous villi. 99mTc-labeled human serum albumin scintigram showed abnormal radioactivity in the small intestine 90 minutes after intravenous injection, indicating protein-losing enteropathy. Hypoalbuminemia was ameliorated by glucocorticoid therapy, but recurred twice when glucocorticoid treatment was tapered. Hypoalbuminemia has not occurred since intestinal lymphangiectasia was improved with glucocorticoid treatment. Levels of elastase 1 and lipase were high in serum and ascites on admission. Endoscopic retrograde pancreatogram showed no abnormalities. Serum pancreatic enzymes were also ameliorated by glucocorticoid therapy, but slightly high levels continued for about one year and a half. This case might have been diagnosed as systemic lupus erythematosus although mixed connective tissue disease was also suspected. There are few reports of protein-losing enteropathy and pancreatic involvement associated with connective tissue diseases. Protein-losing enteropathy and pancreatic involvement were ameliorated with glucocorticoid treatment, suggesting participation of immunological mechanisms.

Connective Tissue Diseases↗

Complement-dependent induction of DNA synthesis and cell proliferation in human liver connective tissue cells in vitro.

Liver connective tissue cells (LCTC) isolated from patients with fibrotic livers have morphological and biochemical characteristics of myofibroblasts. We have examined the proliferation of LCTC derived from normal livers and from livers with fibrosis of different etiologies, as well as proliferation of skin fibroblasts. We have compared proliferation rates in the presence of fresh human serum and heat-inactivated serum. While skin fibroblast and LCTC from normal liver showed no difference, proliferation of LCTC from fibrotic livers was markedly decreased in the presence of heat-inactivated serum. We demonstrate that the native complement component C1 is a factor involved in the induction of DNA synthesis and proliferation of LCTC isolated from fibrotic livers. We propose that native C1, acting probably in cooperation with other growth factors, is involved in the expansion of connective tissue cells during the development of liver fibrosis.

Blood↗