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Female urinary stress incontinence in terms of connective tissue biochemistry.

The role of connective tissue in the aetiology of female stress incontinence has been investigated. Collagen content and extractability as well as estrogen receptor concentration in vesico-vaginal fascia were measured after small tissue biopsies had been obtained during vaginal repair surgery in cases of urinary incontinence. The mean concentration of estrogen receptor in vesico-vaginal fascia among incontinent women was 49.4 +/- 14.8 fmol/mg of protein as compared to 29.6 +/- 13.1 in continent control group (P < 0.03; t-test). The mean hydroxyproline concentration in vesico-vaginal fascia of incontinent women was 13.8 +/- 2.6 micrograms/mg wet weight, whereas in the control group it was significantly higher 20.6 +/- 2.4 (P < 0.001). The role of connective tissue components in the aetiology of female stress incontinence is discussed.

Biomechanical Phenomena↗

Muscle fiber orientation and connective tissue content in the hypertrophied human heart.

To elucidate the structural correlates of cardiac failure in myocardial tissue, muscle fiber alignment and connective tissue volume fraction were measured at multiple sites in the left ventricular free wall and in the interventricular septum of 14 human hearts. Group 1 (five hearts; 280 +/- 20 gm.) had no evidence of cardiac disease, group 2 (five hearts; 380 +/- 30 gm.) had a history of systemic hypertension without clinical heart failure, and group 3 (four hearts;; 590 +/- 40 gm.) had both left ventricular overload and congestive failure. Fiber orientations were determined by measuring fiber angle relative to the circumferential direction (helix angle). The fraction of the myocardial volume occupied by connective tissue was determined by point counting. Our results indicate a smooth transition of helix angle from epi- to endocardial surface in the normal left ventricular free wall with nearly 55 per cent of the wall occupied by circumferentially oriented fibers near the cardiac equator (latitude of largest ventricular diameter); morphologically, the interventricular septum was nearly identical with the free wall. Fiber alignment was maintained in all three groups as was the fraction of wall occupied by circumferential fibers. Connective tissue volume fraction was, however, significantly increased (p less than 0.02) in hypertrophied hearts (groups 2 and 3) as compared with normal hearts, and at two of six sites in clinically failed hearts as compared with hypertrophied but functionally compensated hearts. Thus, muscle fiber orientation is not altered in the hypertrophied pressure-overloaded left ventricle, whereas connective tissue content is increased with the increase being greatest in the failing heart.

Adult↗

How important is tumour shape? Quantification of the epithelial-connective tissue interface in oral lesions using local connected fractal dimension analysis.

Quantification of the local complexity of the epithelial-connective tissue interface (ECTI) in normal mucosa, epithelial dysplasia, and squamous cell carcinoma of the floor of the mouth was investigated by estimating the local connected fractal dimension in tissue profiles from histological sections. The use of certain parameters of the distribution of the local connected fractal dimensions of the ECTI classifies the cases belonging to these three histopathological diagnoses with 85 per cent accuracy by means of linear discriminant analysis. The values of the local fractal dimension were also used to produce colour-coded dimensional images of the ECTI, to highlight locations with higher irregularity that may correlate with locally invasive 'higher-risk' areas.

Carcinoma, Squamous Cell↗

Ameloblastic fibroma with dentinoid formation/immature dentinoma. A microscopic and ultrastructural study of the epithelial-connective tissue interface.

The epithelial-connective tissue interface in an ameloblastic fibroma with dentinoid formation shows four characteristic features: epithelium which is surrounded by a cellular stroma, by a cell-free zone, by a cell-free zone consisting of an amorphous hyaline-like material, and by a dentinoid material. The ultrastructure of these four characteristics resembles stages of the developing tooth. The cellular epithelial-connective tissue interface corresponds to early development before the "bud cap" stage described by Sisca and Provenza (1972). The cell-free zone resembles the "bud cap" stage, and the amorphous layer the "intermediate bell" stage, whereas the interface with dentinoid material has all the features of the "late bell" stage, except for the absence of calcification.

Child↗

Course of mixed connective tissue disease in children.

Mixed connective tissue disease (MCTD) was first reported 25 years ago. This report provides an assessment of the course of juvenile (J) MCTD in 224 patients available in the literature until 1996, including our own 33 patients. Most patients improved and remissions were observed in 3-5% (up to 27%). Among the long-term problems, a loss in joint function was seen in up to 29% of the cases, renal involvement in up to 47%, restrictive lung disease in up to 54% and gastrointestinal manifestations consisting of oesophageal dysmotility in up to 29%. Cerebral involvement was rare but severe. Cardiovascular problems observed include cardiomyopathy, myopericarditis and pulmonary hypertension. Among other long-term problems were Raynaud's phenomenon and scleroderma-like skin changes in up to 86% of the patients. Seventeen of the 224 patients had died (7.6%) because of sepsis or infection (7), cerebral complications (3), heart failure (2), pulmonary hypertension (2), renal failure (2) or gastrointestinal bleeding (1). The mortality rate of JMCTD seems to be in the same range as that of juvenile systemic lupus erythematosus, dermatomyositis and scleroderma. When compared with the other connective tissue diseases, however, mainly minor long-term problems are seen in the surviving patients.

Child↗

Mixed connective tissue disease in siblings.

Mixed connective tissue disease (MCTD) was diagnosed in a brother and sister, and 18 additional family members spanning three generations were studied to detect evidence of autoimmune disease. Symptoms or signs of MCTD without complete expression of the disease were found in 8 relatives of the original cases. Antibodies to ribonucleoprotein and high-titer antinuclear antibodies were found only in the affected siblings. Tests for rheumatoid factor were positive in 9 of 17 relatives of the patients; the titers ranged from 1:160 to 1:2560. The brother and sister with MCTD had an identical HLA genotype--11,12/2,12. The same genotype was inherited by 3 of their siblings, who had impressive rheumatic complaints. This report emphasizes the association between inflammatory connective tissue disease and a specific HLA type within a single kindred.

Adult↗

Relationship of acupuncture points and meridians to connective tissue planes.

Acupuncture meridians traditionally are believed to constitute channels connecting the surface of the body to internal organs. We hypothesize that the network of acupuncture points and meridians can be viewed as a representation of the network formed by interstitial connective tissue. This hypothesis is supported by ultrasound images showing connective tissue cleavage planes at acupuncture points in normal human subjects. To test this hypothesis, we mapped acupuncture points in serial gross anatomical sections through the human arm. We found an 80% correspondence between the sites of acupuncture points and the location of intermuscular or intramuscular connective tissue planes in postmortem tissue sections. We propose that the anatomical relationship of acupuncture points and meridians to connective tissue planes is relevant to acupuncture's mechanism of action and suggests a potentially important integrative role for interstitial connective tissue.

Acupuncture↗

[Echocardiographic study of the heart in children with mitral valve prolapse and connective tissue dysplasia].

Altogether 125 children with connective tissue dysplasia and mitral valve prolapse were subjected to clinical and echographic examinations. Dilation of the aortic root, elevation of pulmonary artery pressure and derangement of myocardial contractility were discovered. These disorders occurred as a result of disseminated connective tissue abnormalities. It is noted that children with connective tissue dysplasia and mitral valve prolapse require prophylactic medical examination because of progressive alterations on the part of the cardiovascular system with age.

Adolescent↗

The influence of differing connective tissue substrates on the maintenance of adult stratified squamous epithelia.

The interaction between adult stratified squamous epithelium and its supporting connective tissue possibly involves both permissive and directive influences. To examine the effect of vitality and specificity of connective tissue on the maintenance of epithelial structure and histodifferentiation, specimens of skin and oral mucosa from various regions of adult mice were separated using either EDTA or trypsin. Prior to transplantation, the epithelium was recombined with either inverted homologous connective tissue or with connective tissue that had been killed either by heating or repeated freeze-thawing. Epithelial sheets were also transplanted onto the graft bed alone or in combination with striated muscle or tendon. Normal patterns of cytodifferentiation were maintained when the epithelium was recombined with inverted or frozen-thawed subepithelial connective tissue but there was a loss of spatial organization on the frozen-thawed connective tissue. In contrast, heat-killed or trypsin-treated frozen-thawed subepithelial connective tissue and non-dermal connective tissue failed to maintain a viable epithelium. These observations suggest that subepithelial connective tissues (dermis, lamina propria) but not deep connective tissues facilitate epithelial proliferation and histodifferentiation.

Animals↗

Panniculitis in connective tissue disease.

Specific and nonspecific panniculitis occur in connective tissue diseases. Microscopic studies of the epidermis and dermis, immunofluorescent microscopy, and extensive serologic testing may aid in the diagnosis and classification of these unusual syndromes. Connective tissue panniculitis and focal lipoatrophy may be forms of immunoreactive panniculitis or connective tissue disease (or both) in which typical microscopic, serologic, or other events related to classic connective tissue disease have not occurred.

Adult↗

Connective tissue growth factor is directly related to liver fibrosis.

BACKGROUND/AIMS: Connective tissue growth factor is a mitogenic, chemotactic, and cell matrix-inducing factor for fibroblasts, and is exclusively and directly induced by transforming growth factor-beta 1. In skin fibrosis, connective tissue growth factor is thought to be a downstream effector of transforming growth factor-beta 1 that is directly involved in the proliferation of connective tissue cells and the accumulation of matrix. Our aim is to confirm the involvement of connective tissue growth factor in liver fibrosis. METHODOLOGY: Specimens obtained from autopsy of 12 patients with normal liver (n = 3), hepatocellular carcinoma (n = 3), liver cirrhosis secondary to alcoholic abuse (n = 3), or viral hepatitis (n = 3), were used for digoxigenin labeled in situ hybridization. RESULTS: Abundant connective tissue growth factor messages were detected in the fibrotic area between cirrhotic nodules. Hepatocytes did not show any signals even when they became carcinomas. Normal livers showed few or no signals. CONCLUSIONS: These results confirmed the direct relationship between connective tissue growth factor gene expression and liver fibrotic change.

Carcinoma, Hepatocellular↗

Development of the connective tissue in the digestive tract of the larval and metamorphosing Xenopus laevis.

Developmental changes, until the completion of metamorphosis, of the connective tissue of the digestive tract in the South African clawed frog Xenopus laevis were examined by light and scanning electron microscopy. During the pre- and prometamorphosis (stages 50 through 59) the layer of connective tissue was prominent in the typhlosole, while that in the rest of the intestine and stomach remained very thin. Most of the connective tissue cells were fibroblasts and were concentrated mainly in the typhlosole, the boundaries of which were distinct. In the anterior part of the typhlosole just behind the stomach, the layers of connective tissue and muscle were the thickest and the boundary between these 2 layers was obscure. Although the mitotic cells of the connective tissue were rare, if any, and no migrating cells were observed on the surface of the connective tissue, the connective tissue of the intestine gradually increased in cell number during the pre- and prometamorphosis. In the stomach, on the other hand, there was no such increase. At the beginning of the metamorphic climax (stages 60 and/or 61), the layer of connective tissue suddenly became thick in both the stomach and the intestine. The boundaries of the typhlosole became less distinct. Mitotic index of the connective tissue became high, and its cells dramatically increased in number and contained many undifferentiated mesenchyme-like cells. In the stomach, these connective tissue cells invaded the glands of the larval epithelium into just below the surface epithelium and mitotic index of the entire stomach epithelium increased. In the intestine, in contrast, mitotic epithelial cells were localized in the islets which invaginated into the connective tissue and later formed the adult epithelium. With the growth of islets, the intestinal folds were formed as straight rows and, after stage 63, were modified into a zigzag pattern and had mitotic cells localized in the troughs of folds. The present results indicate that dramatic changes of the connective tissue of both the stomach and the intestine occur at the beginning of the metamorphic climax, concomitantly with those of the epithelium. Moreover, the results also show that, before the climax, even when there were no indications of metamorphic changes in the epithelium, cells of the connective tissue gradually increased in number in the intestine (but not in the stomach). It is also suggested that the muscle cells of the typhlosole just behind the stomach may participate in this gradual increase of connective tissue cells.

Animals↗

Proliferative responses of endothelial cell populations to experimentally induced inflammatory lesions of gingival connective tissues in the cynomolgus monkey (Macaca fascicularis).

BACKGROUND: Endothelial cells exhibit heterogeneous and tissue-selective responses to injury and inflammation. The regulation of the size of endothelial populations in specific tissue sites is poorly characterized, particularly in soft connective tissues adjacent to bone. To investigate the effect of a primarily lymphocytic infiltrate on endothelial cell proliferation and growth of blood vessels, a primate model was used that reliably exhibits localized, distinct inflammatory, and destructive lesions in isolated sites of mucosal connective tissues adjacent to bone and epithelium around teeth. METHODS: Three Cynomolgus monkeys with healthy periodontium and two with spontaneously occurring inflammation or induced connective tissue destruction were pulse labeled with 3H-thymidine. Morphometric analyses of radioautographs from mid-sagittal supra-alveolar gingival connective tissues of incisor teeth were performed in sites subjacent to junctional, sulcular, and oral epithelium, in the body of the lamina propria and just superior to the alveolar bone crest. RESULTS: Subjacent to the sulcular epithelium there was a statistically significant (P < 0.01) increase in lymphocyte density between health and inflammation. The percentage of endothelial cells incorporating 3H-thymidine label (LI) and the number of blood vessels per unit area were significantly increased in this same site in inflamed samples (P < 0.02) but were not elevated further in lesions in which there was destruction of soft connective tissues. However, there was no increase of the numbers or the cross-sectional areas of blood vessels between samples of inflamed and destroyed tissues. CONCLUSIONS: 1) Experimentally induced inflammation and connective tissue destruction in the gingival connective tissues of Cynomolgus monkeys is associated with site-specific perturbations in the turnover of endothelial cells that is closely linked to lymphocytic infiltration; 2) the vascular response is a generalized increase in endothelial cell proliferation and blood vessel numbers but not lumen size or number of endothelial cells, suggesting the existence of homeostatic controls for preservation of the whole population in a steady state.

Animals↗

Elevated aqueous humour tissue inhibitor of matrix metalloproteinase-1 and connective tissue growth factor in pseudoexfoliation syndrome.

BACKGROUND/AIMS: Pseudoexfoliation syndrome (PXF) was recently found to be associated with increased expression of transforming growth factor beta(1) (TGFbeta(1)) in the aqueous humour. As concern has been raised regarding anti-TGFbeta therapy, which can potentially disrupt the maintenance of anterior chamber associated immune deviation, the authors explored the levels of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), and connective tissue growth factor (CTGF) in aqueous humour to determine if these may represent alternative therapeutic targets. METHODS: Aqueous humour samples were collected from patients who underwent routine cataract surgery. All patients were categorised into three main groups-PXF, uveitis, and control. The PXF group was further subcategorised into three grades based on the density of the exfoliative material observed on biomicroscopy, as well as the presence or absence of glaucoma. TIMP-1, MMP-9, and CTGF levels were measured using specific enzyme immunoassays (ELISA). RESULTS: Eyes with PXF had significantly higher aqueous humour TIMP-1 concentration (n = 56, mean (SE), 9.76 (1.10) ng/ml) compared with controls (n = 112, 5.73 (0.43) ng/ml, p<0.01). Similarly, the CTGF level in PXF eyes (n = 36, 4.38 (0.65) ng/ml) was higher than controls (n = 29, 2.35 (0.46) ng/ml, p<0.05). Further, the CTGF concentration in the PXF glaucoma group is significantly higher compared with PXF eyes without glaucoma (6.03 (1.09) ng/ml v 2.73 (0.45) ng/ml, p<0.01). The MMP-9 levels were low and below detection limit in all PXF and control samples with no statistical difference between groups. CONCLUSION: A raised TIMP-1 level and a low MMP-9 level in aqueous humour of PXF eyes may imply a downregulation in proteolytic activity. The increased CTGF concentration supports the proposed fibrotic pathology of PXF. Regulation of MMP/TIMP expression and anti-CTGF therapy may offer potential therapeutic avenues for controlling PXF associated ocular morbidity.

Aged↗

Development and organization of the pelvic connective tissue in the human fetus.

The developmental changes in the pelvic connective tissue were studied in 200-600 microns sections through the pelves of human fetuses and newborn children, plastinated with an epoxy resin. Three periods are important for the differentiation of the pelvic connective tissue in fetuses. During a first or mesenchymal period (9-12-week-old fetuses), all pelvic regions identical with the so-called pelvic spaces in the adult are filled with loose undifferentiated mesenchyme. Some pelvic organs are covered by a layer of condensed mesenchyme which later constitutes the connective tissue sheath of these organs. During a second or fibrous period (13-20-week-old fetuses), dense connective tissue predominates. It is arranged in circular and semicircular systems covering the rectum, the bladder and the urethra as well as the peritoneal pouches. The arrangement of dense connective tissue is the same in the male and in the female fetus. No ligaments were found within the pelvic cavity apart from the pubovesical and the puboprostatic ligaments. The connective tissue sheaths of the pelvic organs differ from one another. At the level of the pelvic floor only some of them are directly connected with the parietal pelvic fascia. The pelvic spaces are filled by loose connective tissue. During a third or adipose period (21-38-week-old fetuses) adipose tissue develops within the different compartments of the pelvic cavity so that the clear organization found during the second period is abolished.

Abortion, Induced↗

The connective tissue in livers of children.

The amount of connective tissue present, relative to the amount of parenchymal tissue, has been assessed in a random series of 200 livers from children dying from non-hepatic disease. The amount of connective tissue in the left liver is approximately twice that in the right liver. The connective tissue in both lobes progressively diminishes during childhood but at all times remains higher than that in adults.Increased amounts of connective tissue in the liver in children is probably non-specific and related to the degree and duration of shock and hypoxia in the immediate postnatal period.

Age Factors↗

Foetal connective tissue regeneration. A biochemical study in rabbits.

Foetal connective tissue regeneration was studied by implanting 3 x 10 mm cylindrical viscose cellulose sponges subcutaneously in foetal, newborn, and full-grown rabbits. The implants were removed 2 to 7 days later, the foetal implants all being removed after delivery, and were analysed biochemically. In foetal implants a rapid accumulation of soluble forms of collagen took place, while the relative amount of other tissue proteins remained rather low. Connective tissue regeneration of the newborns ressembled, in this respect, that of the full-growns. The results suggest an enhanced production of miniature type collagen in the context of foetal connective tissue regeneration.

Animals↗