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Effect of Tissucol on connective tissue matrix during wound healing: an immunohistochemical study in rat skin.

Fibrin sealants are very useful in different surgical fields. Fixation of free gingival grafts, root coverage procedures, and other techniques increasing connective tissue attachment may be associated with the application of Tissucol in periodontology. The aim of this study was to evaluate the influence of the fibrin sealant in the extracellular matrix, as well as alterations of the connective tissue matrix during wound-healing processes. In the back dermis of 15 Net male rats, Tissucol was implanted after intraperitoneal anesthesia. The implant material was placed in subcutaneous pockets (2 cm in length) which were sutured with interproximal sutures (test and control pockets). At 4, 7, 14, 21, and 28 days after surgery, biopsies of the healed and surrounding tissues were taken, frozen in liquid nitrogen, and examined histologically and immunohistochemically with antibodies against collagen types I, III, IV, V, VI, and VII. The findings showed thick and thin collagen type I and III fibers, respectively, with different orientations localized around the implant material. An increased amount of blood vessels and capillaries (their basement membranes containing collagen type IV) was observed during wound healing which may be associated with the implantation of the sealant. Collagen type V fibers were localized from the first days to the 4th postoperative week and, without any inflammatory reaction (according to histologic staining), formed a fibrillar extracellular matrix with high collagenase resistance. Collagen type VI showed a microfibrillar pattern of distribution, and collagen type VII was localized in the dermo epidermo junction and very deep in the connective tissue in the form of anchoring fibers (only in the test group) during the 4 postoperative weeks of healing. The data showed that Tissucol is a biocompatible component which cannot produce any extensive inflammatory reaction in the matrix. New blood vessel formation, an epithelial-connective tissue interface with high stability, as well as matrix alterations with high resistance in the proteolytic enzymes (i.e., collagenases) can be induced in the connective tissue after use of a fibrin sealant. All of these characteristics may be of great importance in connective tissue healing in periodontal surgical procedures.

Animals↗

Connective-tissue macromolecules in Golgi chicken tendon organs and at their interface with muscle fibers and adjoining tendinous structures.

Tendon organs from leg and forearm muscles of white leghorn chickens were examined with a library of monoclonal antibodies to determine the composition of their connective-tissue framework and the types of connective-tissue macromolecules that occur at the sites where muscle fibers attach to the receptors. The capsules of the tendon organs were positive for connective-tissue macromolecules typical of basal lamina (collagen type IV, laminin, and heparin sulfate proteoglycan) and for tenascin, collagen types III and VI, and fibronectin. Connective-tissue bundles in the lumen of a receptor reacted primarily with antibodies against collagen type I and 4-chondroitin sulfate. The narrow partitions that divide each lumen into compartments stained for collagen type III. Toward its tendinous end, a receptor made few contacts with muscle fibers. Instead, the capsule and the collagenous bundles blended gradually with the intermuscular portions of tendons. At the muscular end, the connections were more complex. Muscle fibers that attached in series to tendon organs split to produce basal lamina-covered, finger-like extensions, which were separated from each other by fissures. Tongues of connective tissue containing tenascin, collagen types I and VI, and fibronectin extended into the fissures. Distally the tongues were continuous with the tenascin in the capsule and just internal to the capsule, fibronectin and basal lamina macromolecules in the capsule, and collagen type I in the collagenous bundles. The uninterrupted presence of these macromolecules around terminating muscle fibers and in the capsule and/or the intraluminal collagen bundles suggests that muscle fibers that attach in series at the muscular end exert a force during muscular contraction on the intraluminal collagen bundles and on the receptor capsule.

Animals↗

Skin is a window on heritable disorders of connective tissue.

A skin biopsy contains the macromolecules present in most connective tissues: collagens, elastin, glycoproteins, and proteoglycans. The specific combination and assembly of these matrix components and their interactions with other structures (e.g., epidermal appendages, nerve and vascular networks) and cells are responsible for the distinction among specific regions of the dermis. The matrix components are interactive and interdependent and modification of one of them, by extrinsic (environmental) and/or intrinsic (systemic, genetic, age-related) factors, may have consequences on the tissue as a whole. The skin, therefore, provides a window through which it is possible to examine how mutations in one connective tissue macromolecule can change the interactions among matrix components and affect tissue structure and organization. Light and electron microscopic studies of skin from patients with inherited connective tissue disorders (e.g., Ehlers-Danlos syndrome, osteogenesis imperfecta, Marfan syndrome, cutis laxa) have led us to the following generalizations about what components change, how individual collagen or elastic fibers are altered and how individual alterations affect overall dermal organization: 1) There is a limited change in the repertoire of collagen fibrils in the skin; 2) there appears to be a greater range of abnormal structure in dermal elastic fibers than in the collagen fibrils; 3) the morphology of the fibroblastic cells may provide clues to the defect in matrix components; 4) similar structural abnormalities result from different molecular defect; 5) a molecular defect in one connective tissue molecule has consequences for the structural properties of other connective tissue components; and 6) although structural alterations in connective tissue fibers are rarely specific for a given disease, there are characteristic patterns of structural change in the matrix that may be used to confirm a diagnosis. These generalizations show that mutations rarely affect only a single aspect of macromolecular function and because of the interactions of matrix components in this complex organ (skin) often disturb the organization of the entire dermis. Genotype-phenotype relationships are important to understand if effective therapies are to be designed. The structure of skin should provide the next level of integration in our efforts to determine how mutations produce disease.

Collagen↗

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↗

The human optic nerve: fascicular organisation and connective tissue types along the extra-fascicular matrix.

Fibres in the mammalian optic nerve are arranged into fascicles between which there is an extra-fascicular matrix containing connective tissue, a feature similar to that found in association with fibres in peripheral nerves, but not otherwise found in the CNS. The relationship between these major features of the nerve architecture are not known. We have addressed this question by examining the fascicular organisation of the optic nerve and the distribution of connective tissue and specific collagen types in the human. We have also examined the spatial development of connective tissue in the human nerve to determine when and from where it originates. Fibres are grouped into fascicles at all locations along the nerve, except intracranially, close to the chiasm where this pattern is lost. Relatively large fascicular numbers are found directly behind the eye and in the region of the optic canal, but decline in the mid-orbital segment of the nerve. Connective tissue is present in the extra-fascicular matrix throughout the fasciculated segment, but in many cases it does not fully encircle fascicles. The proportion of matrix occupied by connective tissue is similar along the length of the nerve (approximately 60%). Within the matrix, collagen types I, III, IV, V and VI are present throughout fasciculated regions. Staining for types V and VI appeared relatively weak compared with that for the other types. Although the collagen types in the nerve are similar to those at the lamina cribrosa and in peripheral nerves, they did not appear to be differentially distributed as in regions of the PNS. Connective tissue enters the nerve at a number of wide-spread locations early in development, consistent with the notion that it enters the nerve with the blood supply. It is present within the matrix before it is established at the lamina cribrosa.

Aged↗

Connective tissue influences on patterns of epithelial architecture and keratinization in skin and oral mucosa of the adult mouse.

Epithelial-mesenchymal interactions play an important role during embryogenesis but it is uncertain whether such interactions influence the maintenance of epithelial structure in the adult. To examine this problem, separated epithelial and connective tissue components of skin and mucosae from various regions of adult mice were homo-or heterotypically recombined and transplanted to histo-compatible hosts. The patterns of tissue architecture and keratinization of the resultant epithelia were examined for changes indicative of mesenchymal influences on the epithelial phenotype. Each type of epithelium, in some recombinations, fully conserved its normal pattern of phenotypic expression indicating that subepithelial connective tissue from all regions is permissive and that regionally-specific connective tissue influences are not necessary for conservation of epithelial specificity. In other recombinations, however, the epithelium acquired features of tissue architecture or keratinization typical of the epithelium normally associated with the connective tissue component, indicating directive influences from the connective tissue. The patterns of epithelial response observed suggest that there may be separate connective tissue influences on epithelial architecture and cyto-differentiation and that there is a regionally-related variation in the competence of epithelia to respond to these influences.

Animals↗

A prospective study of Raynaud phenomenon and early connective tissue disease. A five-year report.

To define features of patients with Raynaud phenomenon that predict the evolution of connective tissue disorders, a prospective study was initiated. Patients with history or physical evidence of Raynaud phenomenon without causal or associated disorders underwent initial multisystem evaluation. Scleroderma (systemic sclerosis) of less than five years' duration was included for comparison. Patients were classified as having Raynaud phenomenon "only," undifferentiated connective tissue syndrome or scleroderma. Nailfold capillary microscopy was performed, and patterns were scored blindly from coded photographs. Of 91 patients with Raynaud phenomenon entered (Raynaud phenomenon only, n = 49; undifferentiated connective tissue syndrome, n = 22; scleroderma, n = 20), abnormal "scleroderma pattern" capillaries were noted in seven of 49, 19 of 22 and 19 of 20, respectively (p less than 0.005). Of 39 patients with Raynaud phenomenon only followed (mean duration, 23.7 months) undifferentiated connective tissue syndrome developed in three. Of 17 patients with undifferentiated connective tissue syndrome followed (mean duration, 27.6 months), six patients had transitions (four scleroderma; one scleroderma-systemic lupus erythematosus overlap; one SLE). Nailfold capillary abnormalities best identified transitional patients in both groups (eight of nine) and were more sensitive than ANA (six of nine), presence of digital ulcers (four of nine) or decreased esophageal motility (two of nine). This prospective study documents a useful role for capillary examinations in evaluating Raynaud phenomenon. Abnormal capillaries indicate an increased risk for connective tissue disease; normal capillaries favor idiopathic Raynaud phenomenon.

Capillaries↗

Quantitative alterations in intramuscular connective tissue following immobilization: an experimental study in the rat calf muscles.

The purpose of the present investigation was to study the effect of immobilization in two different positions, shortened or lengthened, on the connective tissue and capillarization of the rat calf muscles. In 18 rats the left hind limb was immobilized so that the soleus and gastrocnemius muscles were in a lengthened position and tibialis anterior was in a shortened position, and in 18 rats vice versa. The right hind limbs were kept free to serve as controls. After 1, 2, and 3 weeks of immobilization, an equal number of rats were killed and the muscles were analyzed. The connective tissue muscle ratio was measured from histological sections by automatic image analyzer and the number of capillaries per 1000 muscle fibers was also recorded. In the intact muscles the proportions of intramuscular connective tissue in the soleus, gastrocnemius, and tibialis anterior were 2, 3, and 5%, respectively. During the immobilization period of 3 weeks the proportion of connective tissue increased significantly in all muscles, but the only significant difference between the positions was in the soleus muscle in which more connective tissue was found in the lengthened position, 54% vs 30% in the shortened position. The amount of capillaries decreased significantly during immobilization in all muscles to about 65% of normal capillar density, but the position of immobilization seemed to have no effect on this phenomenon. The increase in intramuscular connective tissue during immobilization seems to occur simultaneously with muscle atrophy and loss of muscle capillarity. The stretched position of immobilization seems to have an additional fibrotic effect if the immobilized muscle, such as soleus, consists mainly of type I fibers generally known to be more vulnerable to disuse atrophy than type II fibers.

Animals↗

Connective tissue metabolism in normal and atrophic skeletal muscle.

The first two enzymes of the pentose-phosphate pathway (G6PD and 6PGD) were studied in rabbit skeletal muscle. Their activities closely paralleled the connective tissue levels in each individual muscle, and they increased in atrophying muscles at the same rate as connective tissue. Skeletal muscle tendons and subcutaneously implanted polyvinyl sponges, both of which consist of relatively pure connective tissue, displayed much higher activity of these enzymes than the muscle homogenates. These results suggest that pentose synthesis in muscle is mostly confined to its connective tissue elements, raising the possibility of a role for connective tissue in the biosynthetic processes of skeletal muscle. The contribution of connective tissue to the results of muscle quantitative studies may be significant, and even overshadow other values in atrophic muscles, where the muscle cell population may be greatly reduced. The interpretation of quantitative biochemical studies on pathological muscle samples should take this factor into consideration.

Animals↗

The application of quantitative cytochemistry to the study of diseases of the connective tissues.

The connective tissues are a complex organisation of tissues, cells and intercellular materials spread throughout the body and are subject to a large number of diseases. Such complexity makes the study of the metabolism of the connective tissues in health and more particularly in disease states difficult if one uses conventional biochemical methodology. Fortunately the techniques of quantitative cytochemistry, as developed in recent years, have made it possible to study the metabolism of even such complex and refractory connective tissues as bone. Using properly validated assays of enzyme activity in unfixed sections from various tissues a number of the diseases of the connective tissues have been studied. For example the synovia from patients with rheumatoid arthritis and related conditions have been studied using these techniques and marked alterations in the metabolism of the synovial lining cell population of this tissue have been demonstrated. These alterations in metabolism are believed to be related to the destruction of cartilage and bone found in such diseases. Investigations of the metabolism of the chondrocytes of articular cartilage in a strain of mice which spontaneously develops osteoarthritis has revealed a lack of certain key enzymes of carbohydrate metabolism in precisely those areas where degradation of the matrix of articular cartilage begins suggesting a causal relationship between these events. These same techniques have been used to study the cellular kinetics and metabolism of the dermis and epidermis in the disfiguring disease, psoriasis. The metabolism of healing bone fractures, the diagnosis and treatment of the mucopolysaccharidoses and the metabolic effects of currently used anti-inflammatory and anti-rheumatic drugs have also been examined. Perhaps the most exciting aspect of these studies has been the development and use of the technique of the cytochemical bioassay (CBA) to study hormonally mediated diseases of the connective tissues. Such studies have recently shed new light on the molecular lesion in pseudohypoparathyroidism. Though still in their relative infancy the studies described in this review show the potential inherent in the use of quantitative cytochemistry for the study of diseases of the connective tissues.

Animals↗

Evaluation of different types of autotransplanted connective tissues as potential periodontal ligament substitutes. An experimental replantation study in monkeys.

The purpose of the present study was to investigate connective tissue autotransplants as potential periodontal ligament substitutes. Green Vervet monkeys (Cercopithecus aethiops) were used. Maxillary permanent central incisors were extracted, root filled extraorally and the periodontal ligament removed from the root surface and the socket wall. Two circular cavities were prepared mesially and distally on the root surface. Different types of connective tissue autotransplants were then placed in these cavities, whereafter the teeth were replanted. The animals were sacrificed 8 weeks after replantation and the replanted teeth were examined histometrically. The connective tissue autotransplants were then examined for their capability of preventing root resorption or inducing or forming a new periodontal ligament, including periodontal fibers and cementum. Autotransplanted cutaneous and mucosal connective tissue as well as periosteum and fascia were all found to partially prevent ankylosis by forming a fibrous barrier between the root surface and the alveolus. However, no new cementum was formed. Periodontal ligament transplants, dental follicular tissue and possibly gingival connective tissue were the only tissues capable of both preventing ankylosis and forming a hard tissue on the surface of the cavity with a morphology similar to cementum. It is concluded that cementogenesis requires a highly specialized connective tissue. In this experiment, only odontogenic tissues had this capacity.

Animals↗

[Interstitial lung disease in connective tissue disorders].

Interstitial lung diseases (ILD) associated with connective tissue disorders differ from idiopathic ILD in several aspects, although most of them are comparable. In most patients, ILD occurs during the course, or at the time of diagnosis of connective tissue disease. Opportunistic pulmonary infections, together with adverse effects of treatment should always be discussed. The prevalence of ILD varies among the different connective tissue disorders. Thus, ILD is frequently encountered in patients with systemic sclerosis and to a lesser degree in patients with myositis. As compared to idiopathic ILD, histopathological aspects of ILD associated with connective tissue diseases are more frequently those of non-specific interstitial pneumonia, whereas usual interstitial pneumonia is rare. Other ILD, such as organized pneumonia, interstitial lymphoid pneumonia, diffuse alveolar damage and alveolar hemorrhage are occasionally encountered. ILD must be detected early in the course of collagen disorders by performing computed tomodensitometry and pulmonary function tests. The prognosis of connective tissue associated ILD is better than that of idiopathic ILD. The treatment requires corticosteroids and/or immunosuppressants, depending on the nature of the associated connective tissue disease and ILD progression.

Adrenal Cortex Hormones↗

Organization and distribution of intramuscular connective tissue in normal and immobilized skeletal muscles. An immunohistochemical, polarization and scanning electron microscopic study.

Collagen fiber network is a major contributor to the coherence and tensile strength of normal skeletal muscle. Despite the well-recognized importance of the intramuscular connective tissue to the normal integrity and function of the skeletal muscle, the specific architecture including the location and three-dimensional orientation of the intramuscular connective tissue within the muscle tissue is poorly described. The structure of the intramuscular connective tissue was studied by immunohistochemistry, polarization microscopy (the crimp length and angle of the collagen fibers) and scanning electron microscope (SEM) in rat skeletal muscles (gastrocnemius, soleus and tibialis anterior) in normal situation and after 3 weeks of disuse (immobilization). Three separate networks of collagen fibers were distinguished by SEM in the normal endomysium; fibers running longitudinally on the surface of the muscle fibers (the main collagen orientation), fibers running perpendicularly to the long axis of the muscle fibers and having contacts with adjacent muscle fibers, and fibers attached to the intramuscular nerves and arteries. Similarly, the SEM analysis also disclosed three distinct collagen fiber networks running in different directions in the perimysium, but, contrary to the endomysium, the main fiber orientation could not be established. Immobilization resulted in a marked increase in the endo- and perimysial connective tissue, the majority of the increased endomysial collagen being deposited directly on the sarcolemma of the muscle cells. Immobilization also resulted in substantial increase in the number of perpendicularly oriented collagen fibers with contacts to two adjacent muscle fibers in the endomysium. Further, immobilization clearly disturbed the normal structure of the endomysium making it impossible to distinguish the various networks of fibers from each other. In the perimysium, immobilization-induced changes were similar, the number of longitudinally oriented collagen fibers was increased, the connective tissue was very dense, the number of irregularly oriented collagen fibers was markedly increased, and consequently, the different networks of collagen fibers could not be distinguished from each other. Of the three studied intact muscles, the crimp angle of the collagen fibers was lowest in the soleus and highest in the gastrocnemius muscle, and the crimp angle decreased over 10% in all muscles after the immobilization-period. Altogether, the above described quantitative and qualitative changes in the intramuscular connective tissue are likely to contribute to the deteriorated function and biomechanical properties of the immobilized skeletal muscle.

Animals↗

Epithelial-connective tissue boundary in the oral part of the human soft palate.

The papillary layer of the oral part of the human soft palate was studied in 31 subjects of different age by means of histological, immunohistochemical and scanning electron microscopical methods. For scanning electron microscopy a new maceration method was introduced. Results determine epithelial thickness, height and density of connective tissue papillae and their 3-dimensional architecture inside the lining epithelium as well as the collagenous arrangement of the openings of the glandular ducts. The individual connective tissue papillae of the soft palate are compared with the connective tissue boundary on the other side of the oral cavity. The connective tissue plateaux carrying a variable number of connective tissue papillae were found to be the basic structural units of the papillary body. The function of the epithelial-connective tissue interface and the extracellular matrix arrangement in the lamina propria are discussed in order to promote the comparability of normal with pathologically altered human soft palates.

Aged↗

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↗

An ultrastructural study of connective tissue in mollusc integument: II. Gastropoda.

We studied the ultrastructure of the subepidermal connective tissue (SEC) in different zones of the integument in terrestrial, marine and freshwater gastropods (eight species). In all cases, the SEC was a layer of loose connective tissue between the basal membrane (BM) of the epidermis and the connective tissue of the deeper muscle layers. It was of monotonous structure and not differentiated into layers such as are found in mammalian dermis. The extracellular matrix (ECM) consisted of a network of collagen fibrils of variable diameter, with abundant anchoring devices and proteoglycans. In six species, variables quantities of haemocyanin were present within haemocoelic sinuses present in the SEC. The thickness and density of the BM varied from species to species, as well as within species in the various zones of integument. The ultrastructure of the lamina densa (LD) was indistinguishable from that of BM in bivalves and similar to that in mammals, although basotubules and double pegs were absent. An irregularly spaced lamina lucida was usually present and was often shot thorough with filaments and small protrusions of the LD that connected with epithelial plasma membrane or with hemidesmosomes. A lamina fibroreticularis was not present. LD protrusions characterize the connection between BM and the ECM of SEC. In the terrestrial gastropods, a spongy matrix with ultrastructure closely similar to LD occupied large tracts of the SEC. In the mantle region of Arion rufus, the integumental SEC contained large cavities filled with spherical concretions, probably representing rudiments of a shell. In the mantle where the integument contained abundant muscle fibres, the BM was thick and directly connected to the ECM of the SEC which consisted of compact laminae of collagen fibrils with abundant anchoring devices. Along the edge of the foot of Patella ulyssiponensis, the SEC contained a layer of paramyosinic muscle fibres adhering to the epidermis. No differences or gradations in integumental SEC structure could be related to the phylogenetic position of the species examined.

Animals↗

Epithelial dendritic cells and connective tissue macrophages in oral carcinogenesis and the effects of systemic Corynebacterium parvum.

Epithelial dendritic cells (EDC) and connective tissue macrophages were examined during the induction and growth of oral squamous cell carcinomas in Sprague-Dawley rats treated with the carcinogen 4-nitroquinoline N-oxide (4NQO) and the immune potentiator Corynebacterium parvum. Splenomegaly was induced in all animals receiving C. parvum. Acetone-fixed frozen sections of the palate and tongue were stained using an indirect immunoperoxidase technique and monoclonal antibodies to rat Ia (MRC OX-6) and macrophage subpopulations (ED1, ED2, ED3). EDC were predominantly Ia+, ED1-, ED2- and ED3-. The lamina propria contained Ia+, ED1+ and ED2+ cells; ED3-reactive cells were rare. ED2+ cells predominated in the interstitial connective tissue of deeper muscle. In the non-invasive tissues, the number of positive cells (Ia+EDC and connective tissue Ia+, ED1+ and ED3+ cells) increased significantly throughout the experimental period (0-9 months), were significantly more prevalent in the test tissues (4NQO, 4NQO + C.parvum, C.parvum) compared to untreated controls and, at 9 months, the carcinogen-treated rats (4NQO, 4NQO + C.parvum) had significantly more Ia+ EDC and connective tissue Ia+ cells than C.parvum controls. Irrespective of the marker under study, there were no significant differences between rats treated with 4NQO or 4NQO + C.parvum at any time during the experimental period. Similarly, intra-epithelial Ia+ and ED1+ cells increased significantly throughout the experimental period in all test groups compared to untreated controls, but no significant differences were evident between carcinogen-treated animals (4NQO, 4NQO + C.parvum) and C.parvum controls. Significant positive correlations between connective tissue Ia+ and ED1+ cells and also intra-epithelial Ia+ and ED1+ cells were present in all experimental groups; connective tissue ED2+ and ED3+ cell numbers did not correlate with any of the other phenotypes and intra-epithelial ED2+ and ED3+ cells were rare/absent. Palatal and/or lingual tumours developed in 80% of carcinogen-treated rats by 9 months and the tumour incidence was similar in rats treated with either 4NQO or 4NQO + C.parvum. There were no significant differences in the number of Ia+ EDC between the infiltrating and the non-invasive overlying epithelium of the lingual carcinomas and the non-invasive lingual epithelium treated with either 4NQO or 4NQO + C.parvum.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Nitroquinoline-1-oxide↗

Air oesophagogram: a frequent, but not a specific sign of oesophageal involvement in connective tissue diseases.

OBJECTIVE: This study investigates the role of the air oesophagogram in conventional chest X-rays for the diagnosis of oesophageal dysmotility in patients with connective tissue diseases. METHODS: Fifty-one patients with connective tissue diseases were studied by oesophageal manometry and lateral and posterior-anterior chest X-rays. The presence or absence of oesophageal air on chest X-rays were evaluated separately in the upper, middle and distal segment of the oesophagus. Forty-seven chest X-rays of patients without connective tissue diseases, who had undergone manometry for the evaluation of oesophagus-related symptoms and who had normal oesophageal function, were analysed as a control. RESULTS: A total of 23/51 patients with connective tissue diseases showed oesophageal dysfunction in manometry; 16/51 patients (31%) had air in two or more oesophageal segments on the lateral chest X-ray. There was a significant association of manometrically proven oesophageal dysmotility and air in two or three oesophageal segments (P < 0.05; sensitivity 48%, specificity 82%). However, the prevalence of an air oesophagogram showed no significant difference between patients with connective tissue diseases and the control group (10/47; 21%). CONCLUSION: The radiological sign of an air oesophagogram is neither sensitive nor specific enough to omit oesophageal motility studies in patients with connective tissue diseases.

Air↗