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Transforming growth factor (TGF)-beta 1 is a major mediator of liver fibrosis. Connective tissue growth factor (CTGF) mediates TGF-beta 1 pro-fibrogenic effects in vitro, but its in vivo role is unknown. Both TGF-beta 1 and CTGF are overexpressed in hepatic stellate cells during liver fibrosis. We have used antisense oligonucleotides to examine the role of CTGF in carbon tetrachloride-induced liver fibrosis in mice. Mice received carbon tetrachloride together with CTGF or TGF-beta 1 antisense oligonucleotides for 2 weeks (preventive model), or carbon tetrachloride for 2 weeks followed by carbon tetrachloride and oligonucleotides for 2 more weeks (curative model). In both models, CTGF and TGF-beta 1 oligonucleotides decreased by more than 50 percent the mRNA expression of their targets. Type I collagen mRNA was also decreased by about 40 percent in the preventive experiment. Tissue inhibitor of matrix metalloproteinase-1 mRNA expression and fibrotic deposition evaluated by Sirius red staining were not modified in any group. In summary, our results suggest that hepatic stellate cells can be targeted in vivo with oligonucleotides, and that reducing CTGF levels can lead to a decrease in fibrogenesis as shown by the reduction in type I collagen expression. The lack of effect on fibrosis may be due to the persistence of high tissue inhibitor of matrix metalloproteinase-1 expression.
Avascular connective tissues (cartilage, discs, cornea) change with maturation and aging, particularly in large animals, where diffusion paths are longest. It is suggested that the changes in such tissues are responses to increasing difficulties in obtaining oxygen. Two almost identical structural polymers are made in these tissues: chondroitin sulphate, which requires large amounts of oxygen for biosynthesis and keratan sulphate, which requires relatively little. The observed balance of these polymers in the tissue is proposed to depend on the control of biosynthesis by the ambient oxygen tension, and/or selective breakdown.
Connective tissue massage (CTM) is a manipulative technique that facilitates the diagnosis and treatment of a wide range of pathologies. Observation and subsequent manipulation of the skin and subcutaneous tissues can have a beneficial effect upon tissues remote from the area of treatment. These effects appear to be mediated by neural reflexes that cause an increase in blood flow to the affected region together with suppression of pain. CTM is becoming accepted more widely as research confirms the claims of an expanding population of practitioners.
Connective tissue disorders have well-known ocular associations that may be presenting features of the disease or occur as complications during the course of the disorder. Keratoconjunctivitis sicca, keratitis, scleritis, uveitis, retinal vasculitis, choroidopathy, and their associations with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, psoriatic arthritis, juvenile idiopathic arthritis, and polymyositis are reviewed.
Connective tissue disorders such as scleroderma, dermatomyositis and lupus erythematosus are autoimmune, multi-system disorders whose clinical manifestations can be restricted to the skin or may involve many organs. The degree and rate of organ system involvement defer, as does the prognosis and rapidity of disease progression. In this article, scleroderma, dermatomyositis and lupus erythematosus will be reviewed in respect to their life-threatening potential.
Connective tissue diseases are the most important organic causes of Raynaud's phenomenon, and systemic sclerosis is the most frequent one. Careful history taking and clinical examination eventually lead to further investigations where capillaroscopy and specific autoantibodies tests have the best performances to reach diagnosis. Our understanding of local regulation of blood flow has been improved discovery of new neuromediators and local substances derived from endothelium. These compounds have direct implications for medical therapy and represent new hopes for the treatment of Raynaud's phenomenon which, however, remains difficult and incomplete for most patients.
Connective tissue diseases (CTDs) typically have a wide spectrum of symptoms that vary widely over time, often requiring a large array of medications and laboratory tests. This presents a challenge in all stages of database development, including the selection of data elements, collection methods, coding of variables, and selection of a relational database with the potential for tracking. There is a distinct need for valid, reliable data in a usable form to assist in the diagnosis, management, and research of CTDs. This article discusses the factors involved, provides examples of data collection tools that are presently used, and suggests how they might be employed by the physician in diagnosis and management of CTDs.
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Connective tissue diseases (CTD) lead to a high prevalence of common cardiac manifestations (pericarditis and myocarditis) and of ischemic coronary events with a considerable increase in cardiac mortality related to premature atherosclerosis. Although there are several techniques able to detect cardiac involvement in CTD patients, the most useful and non-invasive technique is echocardiographic exam which is able to detect not only valvular abnormalities, pericardial diseases and pulmonary hypertension but also left ventricular (LV) systolic or diastolic (regional or global) wall motion dysfunction. It is also well known that transesophageal echocardiography (TEE) can better identify cardiac abnormalities, vegetations and embolic sources. Symptomatic patients with positive stress echocardiographic exam or dipyridamole thallium imaging test should be referred for possible cardiac catheterization, especially if a large ischemic territory is involved. Until now, the echocardiographic evaluation of coronary artery tree consisted of assessing regional and global left ventricular systolic and diastolic function at rest and during pharmacological stress test. Recently, a new echocardiographic noninvasive method that allows direct assessment of coronary flow velocity in the mid-distal portion of left anterior descending artery (LAD) has been developed and validated. Advanced ultrasound technology (high-frequency broadband transducer with second harmonic capability) has now made possible a direct arterial visualization and measurement of coronary artery flow in left anterior descending in CTD patients with the assessment of coronary flow reserve (CFR).
Connective tissue diseases (CTD) are a group of autoimmune systemic diseases that can affect any organ-system in the body. The initial clinical presentations of these diseases overlap, not only with each other, but also with a wide range of other rheumatological and non-rheumatological disorders. Due to these reasons, clinicians depend heavily on the use of the clinical immunology laboratory for the diagnosis of CTD. A large number of tests exist in the laboratory for the investigation of CTD and each test can be performed by a number of different methods, each with its own limitations. Consequently, the significance of the results generated not only has to be interpreted in relation to the clinical picture, but also to the method used to generate the results. Moreover, within the laboratory, there is a hierarchical testing system for the investigation of CTD and if this system is used appropriately, in conjunction with the clinical picture, can result in the diagnosis/exclusion of CTD more efficiently and economically. In contrast, random use of the laboratory tests, combined with limited knowledge of the methods used to carry out these tests, can lead to delay or even misdiagnosis, as well as can lead to wastage of resources. In the following review, we have discussed the various tests that are used in the investigation of CTD, as well as the different methods used to carry out these tests, with the hope that such knowledge would lead to a more efficient and economical use of the clinical immunology laboratory in the investigation of CTD.
Connective tissue disorders (CTD) have a relatively high incidence of pulmonary complications but their delineation has been hampered by difficulties inherent in the diagnostic techniques. One fresh approach to this problem is based on a clustering method that uses data from 8 separate investigations to cluster the patients into 4 distinctly separate categories representing normal nonsmoker, normal smokers, those with active interstitial lung disease and those with bronchiolitis. Using this method, a large group of patients with CTD have been examined to assess the nature and extent of their pulmonary complications. Subjects in the first cluster had a normal test profile across all variables, and included no current active smokers. The normal smoking cluster contained only smokers who had a high total lavage cell number with a relative increase in macrophages and a decrease in lymphocytes. In this group, all respiratory variables were normal with the exception of a mildly depressed DLCO, also known to be associated with smoking. The general characteristics of the active interstitial lung disease cluster was a markedly depressed DLCO indicating impaired gas exchange, and elevated gallium index, bronchoalveolar lavage (BAL) cell number and neutrophil and lymphocyte percentages, all indicating an active inflammatory process. However more careful analysis of this group suggested the presence of 2 subgroups, one with a lymphocytic alveolitis, and another with a neutrophilic alveolitis. The bronchiolitis cluster characteristics were a markedly depressed maximal mid expiratory flow rate and raised BAL lymphocyte percentage and gallium index. The distribution of patients within the cluster groupings suggested that Sjögren's syndrome, often an accompaniment of other CTD, is most frequently associated with pulmonary disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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