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PubMed1999

Early events associated with periodontal connective tissue attachment formation on titanium and hydroxyapatite surfaces.

Endosseous dental implants can support at least three types of biomaterial/connective tissue interfaces: osseointegration, fibro-osseous integration, and periodontal connective tissue attachment. Although a periodontal connective tissue attachment offers distinct advantages, only osseointegration and fibro-osseous integration are at present clinically achievable. Recent studies indicate a periodontal regeneration-competent cell population and an appropriate biomaterial substrate both are required for periodontal connective attachment formation on biomaterial surfaces. We therefore have developed an in vitro model to characterize the effects of various biomaterial substrates on the early events of periodontal connective tissue attachment formation. Primary cultures of periodontal ligament and gingival connective tissue cells were cultured on uncoated (control) and coated (titanium- and hydroxyapatite-coated) tissue culture plastic, and the level of cell proliferation, collagen, and noncollagen protein synthesis, alkaline phosphatase activity, and expression of a 42 kD cementum extracellular matrix protein were measured over 5, 7, and 9 days in culture. While all three substrates supported cell attachment, proliferation, and protein synthesis, only uncoated and titanium-coated tissue culture plastic supported expression of the cementum extracellular matrix protein after 9 days of culture. In addition, the levels of cell proliferation and collagen and noncollagen protein synthesis for cells grown on hydroxyapatite-coated surfaces lagged behind cells cultured on the control or titanium-coated surfaces at each of the three time points. These data suggest that biomaterial substrates markedly can influence the temporal sequence of extracellular matrix proteins associated with periodontal connective tissue attachment formation. In addition to surface composition (titanium versus hydroxyapatite), surface properties (e.g., topography) also may have an effect on periodontal connective tissue attachment formation. This model may be of use in designing biomaterials to support the formation of periodontal connective tissue attachment in vivo.

Animals↗
PubMed1982

Mixed connective tissue disease: an overview.

Mixed connective tissue disease is characterized by overlapping features of classic connective tissue diseases and the presence of antibodies to ribonucleoprotein. Placement of this disorder among the classic disorders still remains controversial. The clinical features, prognosis, and therapeutic features of this syndrome are discussed in this report.

Adolescent↗
PubMed1994

Myelopoietic competence of stroma composed of hepatic granuloma-derived connective tissue cells or skin fibroblasts.

1. Connective tissue cells isolated from hepatic granulomas (GR cells), induced in mouse liver tissue by schistosomal infection, are able to sustain myelopoiesis, while other connective tissue cells such as skin fibroblasts (SF) are not. 2. We compared the ability of SF and GR cells to sustain in vitro proliferation of the FDC-P1 myeloid cell line, dependent upon IL-3 or GM-CSF. 3. Only the GR stroma sustained the proliferation of co-cultured FDC-P1 cells. RT-PCR analysis showed that both cell lines expressed the message for GM-CSF, but not for IL-3. We showed that GM-CSF was produced by, and remained bound to the cell layer through heparan sulfate; this growth factor could be released by high-salt treatment in a biologically active form from both cell types. The same activity could be restored to NaCl-treated GR cells, but not to SF, by incubation with recombinant murine GM-CSF. 4. These results indicate that the ability of connective tissue cells to sustain myelopoiesis depends directly upon the capacity of their heparan sulfate-bearing molecules to bind and present the GM-CSF to the target cells in a biologically active form. Alternatively, a yet unidentified set of cell layer-associated molecules may be required for the positive or negative control of the membrane-bound GM-CSF.

Animals↗
PubMed1992

Cardiovascular manifestations of connective tissue disorders.

Disease processes that involve abnormalities of the connective tissue are protean in their manifestations because of the ubiquitous and crucial function that connective tissue serves in the body. Connective tissue supports of the heart and vascular structures play an integral role in normal cardiovascular performance, and it is not surprising that many connective tissue disorders produce important pathophysiologic processes that affect cardiac and vascular elements. The article focuses on the cardiac and vascular manifestations of hereditary and acquired forms of connective tissue disease. Special attention is focused on the use of imaging modalities and their role in diagnosing cardiovascular pathology produced by collagen disorders.

Connective Tissue Diseases↗
PubMed1983

The effect of chronic inflammation on the composition of collagen types in human connective tissue.

Biochemical alterations in the connective tissue matrix are a common feature of many diseases, and they account in major part for their functional impairment. Such alterations are especially important in acute and chronic inflammatory diseases where they may take the form of degradation of matrix components or their excessive accumulation leading to fibrosis. Although a wealth of morphologic information is available, very little is known about these changes at the biochemical level. Using human gingival tissue as a model, we have carried out studies aimed at assessing the effects of chronic inflammation on the collagen isotypes comprising the connective tissue matrix. Tissue obtained from patients undergoing surgical treatment for periodontitis was separated on the basis of clinical features into healthy and inflamed portions. After confirming the inflammatory status of each specimen histologically, each set of tissue pairs was extracted at 4 degrees C in 0.5 M acetic acid containing 1 mg/ml of pepsin, and the extracted collagens were fractionated with NaCl. Alpha chains were separated by polyacrylamide slab gel electrophoresis, and methods devised for their quantitation. The results showed that the proportions of type I and III collagens present in normal and inflamed tissues did not differ significantly. In contrast, the type V collagen, which accounted for 0.1 to 1.3% of the total collagens present in normal tissue, was increased by 2- to 9-fold in the chronically inflamed tissue. Because of the unique binding and connecting role type V collagen is thought to play, this alteration may have major pathologic and functional significance.

Chronic Disease↗
PubMed1999

The relative amount of epithelium, muscle, connective tissue and lumen in prostatic hyperplasia as a function of the mass of tissue resected.

PURPOSE: The relative amounts of epithelium, connective tissue, muscle and gland lumen in benign prostatic hyperplasia have been reported but they have not been correlated with prostate size. We determine if the relative amount of prostatic tissue varies with prostate size. MATERIALS AND METHODS: Paraffin blocks of transurethrally resected prostate tissue were randomly chosen from the archives of 58 patients with benign prostatic hyperplasia. Two new slides per patient were made and stained with prostate specific antigen or Masson trichrome, respectively. A total of 20 images from each slide were captured using a high resolution camera, digitized and analyzed with computer software for the relative percentage of the various tissue components. RESULTS: As the amount of prostate tissue resected increased from less than 10 to greater than 70 gm. the epithelium had a 4-fold increase from 5.37 to 21.92%, the muscle component had a 42% decrease from 28.46 to 16.62%, the lumen doubled from 7.05 to 14.01% and the connective tissue remained relatively unchanged from 35.58 to 31.53%. There was a statistically significant difference in all components of prostatic tissue except for connective tissue when comparing prostates less than 30 versus greater than 30 gm., including epithelium 6.52 versus 16.10% (p <0.01), muscle 28.45 versus 20.78% (p <0.01), lumen 7.42 versus 14.58% (p <0.01) and connective tissue 35.74 versus 32.45% (p <0.06). The stroma-to-epithelium and muscle-to-epithelium ratios each had a 9-fold decline (p = 0.01). CONCLUSIONS: As the prostate increases in size, there is statistically significant more epithelium and lumen, and less muscle tissue.

Connective Tissue↗
PubMed1982

Immune response to connective tissue components of the basement membrane.

The immune response to connective tissue components of basement membrane (type IV collagen and laminin) and to interstitial collagen (type I) has been examined in human and murine systems. We also examined the role that immunologic sensitization to autologous connective tissue components might play in inducing an inflammatory response resulting in pathologic sequelae. Mice receiving a single subcutaneous injection of 5 micrograms type IV or type I murine collagens, or murine laminin in complete Freund's adjuvant mount a delayed-type hypersensitivity response characterized by a mononuclear cell infiltrate when challenged in the footpad with the sensitizing antigen. Cell-mediated immunity to these connective tissue antigens can be transferred to normal syngeneic mice with sensitized T-lymphocytes. In addition, repeated immunizations with these homologous connective tissue components elicit antibody responses in mice. Our data demonstrate the immunogenic nature of types IV and I collagen, and of laminin in a syngeneic murine model. We have demonstrated autoantibodies to the basement membrane and interstitial collagens in the sera of patients with scleroderma (systemic sclerosis); ELISA ratios correlate directly with the extent of pulmonary fibrosis in these patients. Anti-type IV collagen autoantibodies were found to be primarily IgM and anti-type I collagen antibodies, primarily IgG. An antibody response to autologous connective tissue antigens could lead to complement activation, immune complex formation, and deposition of the complexes along vascular endothelium with recruitment of blood monocytes in situ, mirroring the early scleroderma lesion (perivascular mononuclear cell filtrates). In vitro we examined the role of human peripheral blood mononuclear cells in the activation of fibroblasts. Adherent human blood monocytes release mediators which stimulate fibroblast proliferation and collagen deposition. A model is presented for the induction of immunity to autologous connective tissue components, leading to mononuclear cell inflammation, fibroblast activation and fibrosis. Selective immunity to basement membrane collagens may influence the clinical expression of diffuse connective tissue syndromes such as scleroderma (systemic sclerosis).

Animals↗
PubMed1998

Volumetric changes following barrier regeneration procedures for the surgical management of grade II molar furcation defects in baboons: II. Bone, cementum, epithelium, and connective tissue.

In Part I, a computer imaging technique was used to measure the volumetric fill that occurred in surgically created grade II molar furcation defects after they had been treated using the principles of guided tissue regeneration. In Part II, the volumetric fill for each of the specific tissues comprising the defect fill (epithelium, connective tissue, bone, and cementum) was compared. The histologic material consisted of defects treated using one of three types of surgical treatment as well as untreated control sites. All volumetric measurements were expressed as a percentage of the original surgically created defect size, with 100% indicating complete healing of the defect. The results indicate that none of the defects achieved complete healing. Teeth receiving flap debridement had the most overall defect fill (79.50% comprised of 17.13% bone, 35.81% connective tissue, 37.35% epithelium, and 9.71% cementum). Teeth that received a biodegradable barrier showed a mean overall defect fill of 74.98% (7.41% bone, 47.13% connective tissue, 36.20% epithelium, and 9.26% cementum. Sites treated with an exclusion barrier showed 70.75% overall fill (9.63% bone, 40.89% connective tissue, 39.00% epithelium, and 10.48% cementum). The untreated control teeth showed a mean overall fill of 78.70% (5.56% bone, 59.11% connective tissue, 31.06% epithelium, and 4.27% cementum). No significant differences were found among teeth within the same animal and between treatment and controls. The following conclusions were drawn: (1) connective tissue comprised nearly one half of the total fill of the surgically created defects; (2) the percentage of new bone growth was significantly lower than anticipated; and (3) no significant differences were found among the treatment modalities and the untreated control sites for each of the specific tissue types.

Animals↗
PubMed2000

Increased expression of connective tissue growth factor in fibrotic human liver and in activated hepatic stellate cells.

BACKGROUND/AIMS: Connective tissue growth factor is a recently described mitogenic protein implicated in a variety of fibrotic disorders. Connective tissue growth factor may be a downstream mediator of the pro-fibrotic and mitogenic actions of transforming growth factor-beta, promoting extracellular matrix deposition and fibrogenesis. As transforming growth factor-beta is considered important to the pathogenesis of hepatic fibrosis, we examined the possible contribution of connective tissue growth factor to this process. METHODS: Connective tissue growth factor expression was examined in normal and fibrotic human and rat livers using RT-PCR and ribonuclease protection assays, and in primary cultures of rat hepatic stellate cells by Northern and Western blotting. RESULTS: Ribonuclease protection assays demonstrated connective tissue growth factor mRNA was increased 3-5-fold in human fibrotic liver compared with normal. RT-PCR showed this mRNA was increased in carbon-tetrachloride-treated rat liver. Northern analysis showed connective tissue growth factor mRNA was increasingly expressed during progressive activation of cultured rat hepatic stellate cells. Western analysis confirmed that freshly isolated hepatic stellate cells secreted relatively little connective tissue growth factor compared with hepatic stellate cells activated in culture. Hepatic stellate cells stimulated with transforming growth factor-beta showed increased expression of connective tissue growth factor mRNA and protein. CONCLUSIONS: Connective tissue growth factor mRNA is consistently upregulated in human liver cirrhosis of various aetiologies, supporting a role for this growth factor in hepatic fibrogenesis. Our studies suggest that hepatic stellate cells may be an important source of hepatic connective tissue growth factor in vivo, particularly following stimulation with transforming growth factor-beta.

Animals↗
PubMed1999

Genetic susceptibility to the connective tissue diseases.

Genes important in the connective tissue diseases are being recognized in two basic ways: association studies and linkage analysis. Traditionally, association studies have confirmed a genetic influence in disease pathogenesis, especially in systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, and the spondyloarthropathies. One of the strongest associations is with the HLA region. As techniques improve, genome scan studies suggest that multiple genes are involved in each of the connective tissue diseases, with some genes in common that confer an autoimmune susceptibility. Linkage analysis is identifying new candidate genes that will help to explain the etiology of connective tissue diseases.

Connective Tissue Diseases↗
PubMed1998

High-resolution magnetic resonance imaging of the orbital connective tissue system.

A complex system of connective-tissue septa within the orbit has previously been described in serial histologic sections. The present study describes the anatomy of the orbital connective tissue system on high-resolution magnetic resonance (MR) images in vivo. Five volunteers aged 26 to 35 year underwent magnetic resonance imaging of the orbit on a 1 Tesla unit (Impact, Siemens, Germany). T1-weighted coronal images were obtained using a surface coil. Anatomical structures on the MR images were identified by comparison with corresponding histologic sections. On MR images of the anterior orbit, the levator aponeurosis, Lockwood ligament, transverse intermuscular ligament, common sheath, check ligaments, Tenon capsule, intermuscular septa, and palpebral ligaments can be seen. In the mid- and posterior orbit, the intermuscular orbital septa, especially the superolateral septum, the superior ophthalmic vein hammock, and septa of the radial connective tissue system are visualized. High-resolution magnetic resonance imaging is capable of delineating the major septa of the orbital connective tissue system.

Adult↗
PubMed1980

The roles of hyaluronic acid, collagen and elastin in the mechanical properties of connective tissues.

Biomechanical testing of connective tissue is usually done on whole tissue. Studies of the mechanical properties of each component of the tissue, however, are important for elucidating the connection between the functional properties and the molecular structure. Enzymic degradation of one component at a time followed by mechanical testing was employed. The specificity of enzymes used was ascertained with mechanical tests on collagen films from purified, reconstituted collagen after enzymic treatment. The study shows that collagen is the component which is mainly responsible for the tensile strength of skin and aorta, while the toe-part of the 'stress'-strain curve of aorta is determined by both elastin and collagen. The hyaluronic acid does not seem to play any role in the static mechanical properties of skin and aorta as evaluated by means of the present method.

Animals↗
PubMed1977

Histologic changes following the grafting of connective tissue into human gingiva.

Grafting connective tissue from the palate to partial-thickness sites prepared in patients with an inadequate width of attached gingiva resulted in an increased width of keratinized mucosa. Biopsies of these grafts at the newly created mucogingival junction at 24 weeks showed the epithelium to be keratinized with a normal architecture, except over scar tissue at the edges of the grafts, where rete-peg formation was absent. The results support the concept that morphodifferentiation of gingival epithelium is influenced by the underlying connective tissue.

Collagen↗
PubMedDate not supplied

A small angle light scattering device for planar connective tissue microstructural analysis.

The planar fibrous connective tissues of the body are composed of a dense extracellular network of collagen and elastin fibers embedded in a ground matrix, and thus can be thought of as biocomposites. Thus, the quantification of fiber architecture is an important step in developing an understanding of the mechanics of planar tissues in health and disease. We have used small angle light scattering (SALS) to map the gross fiber orientation of several soft membrane connective tissues. However, the device and analysis methods used in these studies required extensive manual intervention and were unsuitable for large-scale fiber architectural mapping studies. We have developed an improved SALS device that allows for rapid data acquisition, automated high spatial resolution specimen positioning, and new analysis methods suitable for large-scale mapping studies. Extensive validation experiments revealed that the SALS device can accurately measure fiber orientation for up to a tissue thickness of at least 500 microns to an angular resolution of approximately 1 degree and a spatial resolution of +/-254 microns. To demonstrate the new device's capabilities, structural measurements from porcine aortic valve leaflets are presented. Results indicate that the new SALS device provides an accurate method for rapid quantification of the gross fiber structure of planar connective tissues.

Animals↗
PubMed1981

Severe pulmonary involvement in mixed connective tissue disease.

Pulmonary involvement in mixed connective tissue disease has been considered a benign manifestation that is easily treated with corticosteroids. We followed 5 patients who had mixed connective tissue disease and severe, rapidly progressive, lung disease. Two types of lung disease were found, interstitial lung disease and pulmonary hypertension. Histologic sections from our patients were compared with sections from patients who had interstitial lung disease and systemic lupus erythematosus or pulmonary hypertension and scleroderma. Although clinical presentations were similar, the immunofluorescent and electron microscopic findings for interstitial lung disease were somewhat different in patients with systemic lupus erythematosus. Histologic findings for pulmonary hypertension appeared different in patients with mixed connective tissue disease and patients with scleroderma. For patients with either type of lung disease, corticosteroid therapy proved inadequate, but nearly cytotoxic therapy may be beneficial.

Adult↗
PubMed1982

The connective tissue of the adult female pelvic region. A microscopical analysis.

Using special histological criteria, structures found during blunt dissection of the adult female pelvic region could be recognized in 0.7-0.8 cm thick transparent histologically stained serial sections of this region, as connective tissue ribbons. The connective tissue in the adult female pelvic region reveals an orderly constructed system of coherent connective tissue ribbons. These ribbons form a skeleton which borders several separate functional areas. Areas for the locomotive system of the leg areas containing the pelvic vessels and viscera are separated by an area of adipose tissue. This area is again bordered by a connective tissue ribbon. In the fossa ischiorectalis also connective tissue ribbons are found, bordering areas filled with adipose tissue. These connective tissue ribbons interconnect the musculus levator ani, the epidermis, the musculus obturatorius internus, and the musculus gluteus maximus. The architecture found in the sections has a bilateral symmetry and possesses interindividual uniformity. The three-dimensional architecture of this system of connective tissue ribbons will be described in a next article.

Adipose Tissue↗
PubMedDate not supplied

[Non SLE connective tissue diseases: general aspects and kidney].

Connective tissue diseases represent a group of heterogeneous disorders that share certain common features, including inflammation of the skin, joints and other structures rich in connective tissue, as well as altered immunoregulation patterns, including autoantibody production and cell-mediated immunity abnormalities. While certain distinct clinical entities can be defined, manifestations can vary considerably from patient to patient, and the overlap of clinical features between and among specific diseases is common. Genetic, environmental and sex hormonal factors are likely to be of pathogenic importance. Among these diseases, systemic lupus erythematosus is the most frequent, followed by systemic sclerosis or scleroderma (SSc), Sjogren's disease, polymyositis and dermatomyositis and mixed connective tissue disease. Systemic sclerosis involves multiple organs in a process consisting of disseminated sclerosis affecting all compartments. Prominent vascular lesions typify the renal lesions. Scleroderma crisis is a major complication of SSc, characterized by severe hypertension, rapidly progressive renal failure, thrombotic microangiopathy with hemolitic anemia and low platelet count: the prompt use of angiotensin-converting enzyme (ACE) inhibitors significantly increased the 1-yr survival rate from 15 to 76%. Sjogren's syndrome is an immunologic disorder characterized by progressive lymphocytic destruction of the exocrine gland, frequently resulting in symptomatic eye and mouth dryness. The interstitial lesions constitute the principal renal manifestations: interstitial infiltrates and small lymphocytes, which can be homogenous and massive. In polymyositis and dermatomyositis renal involvement is rare.

Connective Tissue Diseases↗