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PubMed2004

Connective tissue growth factor and renal diseases: some answers, more questions.

PURPOSE OF REVIEW: Connective tissue growth factor (CCN2) has recently received much attention as a possible key determinant of progressive renal fibrosis. However, the mechanism(s) by which this growth factor functions is not known. The purpose of this review is to summarize and discuss the recent findings regarding the possible mechanisms involved. RECENT FINDINGS: Emerging evidence from in-vitro studies of renal cells indicates that connective tissue growth factor is a crucial mediator for transforming growth factor-beta-induced cellular dysfunction, manifest by increased cellular hypertrophy, synthesis of extracellular matrix proteins and their deposition and assembly around the cells. Indeed, recent evidence suggests that the interrelationship between connective tissue growth factor and transforming growth factor-beta is stronger than first thought. While transforming growth factor-beta induces the expression of connective tissue growth factor, the latter plays a key role in both bioactivation of latent transforming growth factor-beta and the promotion of its Smad signalling activity. SUMMARY: Connective tissue growth factor is clearly implicated in the pathogenesis of progressive renal disease. Although there is much to learn about the production, function, and mechanism of action of connective tissue growth factor, some progress has been made in understanding the molecular basis of its relationship with transforming growth factor-beta. Elucidating the signal transduction pathways activated by connective tissue growth factor will also definitely help to clarify other actions of connective tissue growth factor which may be independent of transforming growth factor-beta. Because of the inflammatory and immunosuppressive properties of transforming growth factor-beta, connective tissue growth factor seems to be an attractive alternative therapeutic target for combating renal fibrosis.

Animals↗
PubMed2003

Network organization of interstitial connective tissue cells in the human endolymphatic duct.

The human endolymphatic duct (ED) and sac of the inner ear have been suggested to control endolymph volume and pressure. However, the physiological mechanisms for these processes remain obscure. We investigated the organization of the periductal interstitial connective tissue cells and extracellular matrix (ECM) in four freshly fixed human EDs by transmission electron microscopy and by immunohistochemistry. The unique surgical material allowed a greatly improved structural and epitopic preservation of tissue. Periductal connective tissue cells formed frequent intercellular contacts and focally occurring electron-dense contacts to ECM structures, creating a complex tissue network. The connective tissue cells also formed contacts with the basal lamina of the ED epithelium and the bone matrix, connecting the ED with the surrounding bone of the vestibular aqueduct. The interstitial connective tissue cells were non-endothelial and non-smooth muscle fibroblastoid cells. We suggest that the ED tissue network forms a functional mechanical entity that takes part in the control of inner ear fluid pressure and endolymph resorption.

Connective Tissue Cells↗
PubMed2005

Evaluation of the safety and efficacy of periodontal applications of a living tissue-engineered human fibroblast-derived dermal substitute. II. Comparison to the subepithelial connective tissue graft: a randomized controlled feasibility study.

BACKGROUND: The subepithelial connective tissue graft, traditionally harvested from the patient's palate, is commonly used for root coverage in periodontal recession defects. This study evaluates the safety and effectiveness of a living human fibroblast-derived dermal substitute (HF-DDS) compared to a connective tissue graft (CTG) for root coverage in these situations. METHODS: Thirteen patients were selected for this study. Each patient had Miller Class I or II bilateral facial recession defects > or =3 mm on two non-adjacent teeth. The test tooth received an HF-DDS graft, while a CTG was placed on the control site. The 10 test surgeries were performed by one operator and three pilot surgeries were performed by another surgeon. Eight of the HF-DDS sites received a single thickness of material; five received a double thickness. Clinical measurements were taken at baseline; 1 week; and 1, 3, and 6 months following surgery. Parameters measured were plaque index, recession depth, clinical attachment levels, recession width, probing depth, and width of keratinized tissue. All clinical readings were taken by a masked, calibrated examiner. RESULTS: There were no statistically significant differences between the test and control groups. The amount of root coverage was slightly greater for the control group than for the test group, but statistically the difference was insignificant. The width of the recession defect measured at the cemento-enamel junction (CEJ) for the test group was slightly smaller than that of the control group at the conclusion of the study. The amount of keratinized tissue was the same in both groups at 6 months. The probing depth was slightly greater in the control group as was the gain in clinical attachment, but neither was statistically significant. The amount of root coverage obtained when one layer of HF-DDS was used compared to the amount of coverage obtained when two layers were used approached statistical significance, but the small sample size may have been responsible for the difference. CONCLUSION: Within the limits of this study, the human fibroblast-derived dermal substitute may offer potential as a substitute to the connective tissue graft for covering areas of facial Miller Class I or Class II gingival recession in humans.

Adult↗
PubMed2002

Ultrastructural connective tissue aberrations in patients with intracranial aneurysms.

BACKGROUND AND PURPOSE: An unknown connective tissue defect might predispose for the development and rupture of intracranial aneurysms in some patients. This study of connective tissue samples of a series of patients with intracranial aneurysms investigates the morphology of the extracellular matrix with methods that are currently used in the routine diagnosis of inherited connective tissue disorders. METHODS: Skin biopsies from 21 patients with intracranial aneurysms, many with multiple aneurysms, were studied by electron microscopy. None of the patients included in this study showed clinical signs of a known connective tissue disorder. RESULTS: In 7 patients (33%), we observed repetitive aberrations in the morphology of collagen fibrils and elastic fibers of the reticular dermis. The observed ultrastructural findings were somewhat similar to those typically observed in patients with Ehlers-Danlos syndrome (EDS) and in a subgroup of patients with spontaneous cervical artery dissections. The patterns of abnormalities fell into 2 classes: 4 patients displayed abnormalities that resembled those found in patients with EDS type III, and the electron microscopic findings in the skin biopsies from 3 patients resembled those of EDS type IV patients. The sequence of the COL3A1 gene from the patients with EDS type IV-like alterations of the connective tissue morphology was analyzed. No mutation was detected. CONCLUSIONS: Connective tissue alterations were found in skin biopsies from a minority of patients with intracranial aneurysms. Electron microscopic investigation of skin biopsies from patients and their relatives might become valuable for clinical diagnostics, identification of persons at risk, and basic studies of the pathogenesis of this vascular disease.

Adult↗
PubMed2003

Inflammation of embryonic connective tissue in the middle ear spaces.

OBJECTIVE: Persistent embryonic connective tissue has been considered to be a cause of chronic otitis media with effusion in neonates and of cholesteatoma in later life. As part of a study of pneumatization and resorption of embryonic connective tissue from the middle ear of pre- and postnatal infants, inflammatory processes of variable extents have been observed within the embryonic connective tissue. The aim of the present study was to characterize this inflammation and to detect patterns in its presence and distribution. MATERIAL AND METHODS: Twenty fetal temporal bones obtained at 4-8 months of development and 31 temporal bones from children who died of sudden infant death syndrome aged < 1 year were studied to assess the inflammation within the middle ear cleft and specifically in the embryonic connective tissue. RESULTS: Sixteen of 27 (59.3%) pre- and 10/31 (32.2%) postnatal specimens displayed a non-specific inflammatory lymphocytic infiltration without signs of bacterial infection or the presence of or reaction to amniotic contents. Eleven of 27 prenatal temporal bones (40.7%) and 16/31 (51.6%) postnatal specimens showed no evidence of histologic middle ear inflammation. The presence or absence of inflammation was independent of age. CONCLUSION: Our observations indicate resorption of the embryonic connective tissue with individual variations indicating that genetic factors are responsible for the development of the middle ear spaces during the phases of development studied.

Acute Disease↗
PubMed1989

[Stereo architecture of the connective tissue papillae of lips and gingiva in newborn dogs].

The surface structure of the connective tissue papillae of lips and gingiva of newborn dogs 1 and 4 weeks after birth were observed by scanning electron microscopy. 1. Long term HCl treatment successfully removed the epithelial cell layer from the connective tissue over a large area of fixed material. 2. Connective tissue papillae of labial skin, labial mucosa and alveolar and gingival mucosa were exposed and it became clear that connective tissue papillae were highly developed at the labial margin and just beneath the gingival margin. 3. In the hair growing area of the labial skin, connective tissue papillae became smaller, and some ridge-like structures were found running vertically. 4. On the lining mucosa such as the labial and alveolar mucosa, the surface of the connective tissue papillae showed only ridge-like structures running vertically. 5. From the results of both light and electron microscopy, we concluded that there was a tendency for the area to have a thick epithelial cell layer which contained highly developed connective tissue papillae. This suggested that the blood vessels in the connective tissue papillae can carry nutrients closer to more epithelial cells penetrating deeply into the epithelium thickness.

Animals↗
PubMed1983

Current concepts in soft connective tissue wound healing.

The strength and integrity of intact soft connective tissues are related to the forces which exist between collagen fibrils and these in turn appear to depend on collagen fibril size, density and architecture en masse. The genetic type of collagen, enzymic modifications to the collagen monomer and the proteoglycan environment all affect fibril size. Current evidence suggests that the restoration of tissue continuity and the early redevelopment of tissue strength following wounding are initially achieved by the formation of a myofibroblast-reticulin network which eventually disappears as the healing wound ages. The extent of this network defines the area in which repair tissue will be laid down and the network is equipped with the sensory apparatus to monitor the physical and chemical environment where healing is taking place and thus to direct the various facets of connective tissue synthesis outlined above. The maturation of the scar connective tissue matrix and the development of attachment between new and original connective tissues are simultaneous, related but independent processes. It takes some time before the weld is achieved by the same forces that hold connective tissue fibres together in intact tissues and the myofibroblast-reticulin network is replaced.

Animals↗
PubMed1984

Discovery of a connective tissue dysplasia in the Martin-Bell syndrome.

The fact that a connective tissue dysplasia is a component of the Martin-Bell syndrome was a fortuitous discovery. A 26-month-old developmentally delayed boy had many signs of a connective tissue dysplasia for which he was referred to a University center where he was found to be fragile (X)-positive without confirmation of a connective tissue problem. Sensitized by these events and observations, we were able to predict at a glance in an unrelated family the fragile (X)-positive status of 2 subsequently referred brothers with mental retardation and prominent manifestations of connective tissue dysplasia. Thus, the Martin-Bell syndrome is an incompletely recessive, pleiotropic trait involving CNS, testes and connective tissues. The characteristic facial appearance of affected males largely represents interaction of mental retardation, congenital CNS based muscle hypotonia and connective tissue dysplasia. At the 1983 NIH workshop on XLMR there was a general consensus that a connective tissue dysplasia is a component of the Martin-Bell syndrome, a fact since confirmed by others on the basis of objective measurements of finger joint hypermobility and frequent presence of mitral valve prolapse.

Abnormalities, Multiple↗
PubMed2003

Esthetic soft tissue ridge augmentation using an acellular dermal connective tissue allograft.

UNLABELLED: Residual ridge defects present significant limitations to the esthetic restoration of edentulous tooth sites. Augmentation techniques can aid in the re-establishment of natural ridge contours. This article describes a technique in which an acellular dermal connective tissue allograft is used to augment a buccolingual residual ridge defect. A single vertical incision enables the allograft to be placed laterally into a buccal pouch. Augmentation of this edentulous site permitted a three-unit bridge to be placed with a highly esthetic pontic. CLINICAL SIGNIFICANCE: This article presents a simplified method of esthetic ridge augmentation that reduces patient discomfort.

Aged↗
PubMed1995

Breast implants, rheumatoid arthritis, and connective tissue diseases in a clinical practice.

This study was designed to assess the relationship between breast implants and certain rheumatologic diseases (rheumatoid arthritis and diffuse connective tissue diseases). The study base was a rheumatological practice in Atlanta, Georgia that started in 1982 and began computerizing its records in 1985. The computerized records through May 1992 included 4229 women patients, 150 with breast implants and 721 with a diagnosis of rheumatoid arthritis (RA) and/or one of the connective tissue diseases (CTDs). Of the 721 patients who had been diagnosed as having rheumatoid arthritis (RA) and/or one of the connective tissue diseases (CTDs), 392 had rheumatoid arthritis, 344 had connective tissue disease, 15 had both rheumatoid arthritis and a connective tissue disease, and 33 had more than one connective tissue disease. Of the patients with connective tissue disease, 179 had systemic lupus erythematosus, 64 had scleroderma, 49 had Sjögren's syndrome, 36 had dermatomyositis or polymyositis, and 49 had mixed connective tissue disease. Data were analyzed by univariate and multivariate techniques including logistic regression. Significant variables included age at first visit, income strata, and period of first visit. Analyses were performed for each clinical diagnosis, for all connective tissue diseases together (CTDs), and for those with rheumatoid arthritis and/or connective tissue disease (RA/CTD). Analyses were performed on the total data base and on the records of new patients (1986-1992). The adjusted odds ratio for breast implants among women who entered the practice in 1986-1992 and were diagnosed as having rheumatoid arthritis and/or one of the connective tissue diseases (RA/CTDs) was 0.45 (0.22-0.90), for those with rheumatoid arthritis was 0.61 (0.28-1.49), for those with any of these specific diffuse connective tissue diseases was 0.34 (0.11-1.06) compared to those without the disease. For systemic lupus erythematosus, the odds ratio of 0.24 (0.03-1.75) was based on a single case who had the disease 5 yr before the implant. For Sjögren's syndrome, the odds ratio was 1.67 (0.39-7.13) based on two cases, one of whom had the disease 5 yr before the implant. The calculated odds ratios for scleroderma, dermatomyositis/polymyositis, and mixed connective tissue disease were zero since no cases were diagnosed among the patients with breast implants. This study found no evidence that women with breast implants are at an increased risk for having rheumatoid arthritis or other diffuse connective tissue disease.

Adult↗
PubMed1975

A complex junctional system in endothelial and connective tissue cells of the choroid plexus.

Endothelial and connective tissue cells of the choroid plexus have been studied by the freeze-etching technique. The endothelial cells of pre- and postcapillary segments are coupled by a complex junctional system consisting of a combination of tight and gap junctions. Connective tissue cells revealed the same intercellular contacts. Furthermore two different types of gap junctions occurring in membranes of the connective tissue cells are described.

Animals↗
PubMed1994

Neurovascular manifestations of heritable connective tissue disorders. A review.

BACKGROUND: Heritable disorders of connective tissue are recognized in a small minority of patients with neurovascular diseases. In this report, we review the neurovascular manifestations of four heritable connective tissue disorders: Ehlers-Danlos syndrome, Marfan's syndrome, osteogenesis imperfecta, and pseudoxanthoma elasticum, as well as two other systemic disorders with potential vascular manifestations: neurofibromatosis and polycystic kidney disease. SUMMARY OF REVIEW: Typical neurovascular complications of Ehlers-Danlos syndrome are carotid-cavernous fistulae, intracranial aneurysms, and cervical artery dissections. Arterial dissections and intracranial aneurysms cause the majority of neurovascular symptoms in Marfan's syndrome. Neurovascular disease is uncommon in osteogenesis imperfecta, although carotid-cavernous fistulae and vertebral artery dissections have been reported. Neurovascular disease in pseudoxanthoma elasticum is characterized by intracranial aneurysms and cerebral ischemia caused by premature arterial occlusive disease. Intracranial occlusive arterial disease is the most common neurovascular manifestation of neurofibromatosis, followed by cervical arteriovenous fistulae and aneurysms and intracranial aneurysms. Intracranial aneurysms are the hallmark of polycystic kidney disease. CONCLUSIONS: Recognition of an underlying generalized connective tissue disorder may be of considerable importance, although marked phenotypic heterogeneity often complicates the diagnosis of these disorders. Conversely, the association of certain neurovascular anomalies with generalized connective tissue disorders and recognition of their basic molecular defect may offer clues to the etiology and pathogenesis of these neurovascular diseases in general.

Cerebrovascular Disorders↗
PubMed1981

Relationships between epithelium and connective tissue in inflamed gingiva.

Since chronic inflammation has been associated with degenerative and proliferative responses in connective tissue and epithelium, it was decided to investigate quantitatively the proportions of epithelium and connective tissue in inflamed gingiva. Forty-five midfacial gingival sites were assessed prior to biopsy for the presence or absence of bleeding after probing using a controlled insertion force fo 25 g. In order to delineate the corresponding area for histologic analysis, a reference incision was made on the facial surface of the gingiva which demarcated the depth and mesio-distal extent of the area probed. Step-serial bucco-lingual sections were morphometrically analyzed to determine the percentages of epithelium, inflamed, and noninflamed connective tissues coronal to the reference incision. The data was compared with respect to the presence or absence of bleeding after probing. Specimens which bled after probing had significantly less epithelium and more connective tissue. The increase in overall connective tissue was due to a significant increase in the inflamed component, and it appeared that the decrease in epithelium corresponded to the increase in inflamed connective tissue. The findings of diminished epithelium overlying inflamed connective tissue reinforces the concept that connective tissue status is important for determining structure and function of epithelium.

Adult↗
PubMed1975

The role of gingival connective tissue in determining epithelial differentiation.

Free grafts of connective tissue, without epithelium, were transplanted from either the keratinized gingiva or the non-keratinized alveolar mucosa (controls) into areas of the alveolar mucosa in seven monkeys. The grafts were placed in pouches created in the connective tissue as close as possible to the overlying epithelium. After 3-4 weeks, the transplants were exposed by removal of the overlying tissue in order to allow epithelialization from the surrounding non-keratinized alveolar mucosa. The transplants were examined clinically and histologically at time peiods between 1 and 12 months. The gingival connective tissue grafts became covered with keratinized epithelium displaying the same characteristics as those of normal gingival epithelium. The alveolar mucosa transplants were covered with non-keratinized epithelium. This indicated that gingival connective tissue is capable of inducing the formation of a keratinized gingival epithelium.

Animals↗
PubMedDate not supplied

[Orbital veins and arteries in relation to the connective tissue system of the orbit].

Our study revealed that the relationships between the vessels and the connective tissue, which forms a constant and bilateral symmetrical system of connective tissue septa bordering adipose tissue compartments, are characteristics and constant but essentially different for veins and arteries. The arteries run within the adipose tissue compartments only contacting the connective tissue septa where they perforate them. As to the veins, their relationship with the connective tissue apparatus is completely different. These vessels run within the septa firmly connected with their connective tissue fibres, forming a continuity between the adventitia of the veins and the walls of the adipose tissue compartments. This difference between arteries and veins results in a different spatial structure for the two vascular systems. The arterial system is a radiating system, whereas the venous system is an anastomosing complex of venous rings which are arranged circularly inside as well as outside the muscle cone. It seems likely that the relationships of the vessels, particularly of the veins, with the connective tissue apparatus play an important role in the well-functioning of the orbital blood-circulation.

Adipose Tissue↗
PubMedDate not supplied

[Effect of infrared laser radiation on sorption of dry cartilage and connective tissue preparations].

Cartilaginous and connective tissues were exposed to a moderate-intensity IR laser treatment with IR radiometric temperature control. The isotherms of water sorption by dry preparations of intact and laser-treated tissues were obtained and calculated in terms of well known models. It was shown that the sorption capacity of a monolayer of tissues decreases with increasing temperature during laser treatment. Changes in the supramolecular structure of the extracellular matrix of tissues (loss of regularity) upon IR laser exposure are discussed.

Animals↗
PubMed2006

Epidemiology of connective tissue disorders.

The reported prevalence and incidence of connective tissue disorders are quite variable, depending on differences in study methodology. Most important differences are the study duration, the classification criteria used for diagnosis and the country in which the study was undertaken. Sjögren's syndrome has the highest prevalence ranging between 0.5 and 3% of a given population. The prevalence of systemic lupus erythematosus (SLE) is estimated between 15 and 50 per 100 000 individuals, with a female:male ratio of 6-10:1 in the age group between 15 and 40 yrs. The prevalence of systemic sclerosis is lower, however, varying significantly between different studies and countries. The prevalence of overlap syndromes, especially mixed connective tissue disease, is unknown, and polymyositis and dermatomyositis are regarded as very rare rheumatic diseases. Though the classification criteria for the connective tissue disorders have not been developed for the purpose of diagnosing an individual patient, these criteria still are the most valuable tool for the identification of patients with systemic rheumatic diseases such as connective tissue disorders.

Adolescent↗