A comparison of connective tissue lining aortic grafts with extravascular connective tissue.
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With the invention of drugs that effectively and specifically inhibit excessive collagen synthesis in the liver, a growing interest in serum assays that assess fibrogenesis, i.e. the de novo formation and fibrolysis, i.e. the removal of connective tissue in the liver, may be anticipated. Several serum assays for connective tissue polypeptides fulfil the criteria of sensitivity and specificity for chronic liver diseases. The aminoterminal procollagen type III peptide (PIIINP) correlates with hepatic fibrogenesis, whereas the propeptides of basement membrane collagen (PIVNP and PIVCP) and the basement membrane glycoprotein laminin reflect the enhanced turnover of basement membranes of the sinusoids as well as of proliferating bile ducts and blood vessels in active fibrosis. Circulating collagen type VI results from degradation of interstitial microfilaments and undulin appears to be released upon remodeling of the hepatic architecture. Combined measurement of selected parameters may allow a non-invasive assessment of the balance between fibrogenesis and fibrolysis on a day-to-day basis, especially in the light of potential antifibrotic therapy.
Differences between advanced gastric cancer of the medullary type (med.: 138 cases) and the scirrhous type (sci: 164 cases) with regard to the amount of connective tissue that was cancerous have been studied clinicopathologically. A correlation was found between med and liver metastasis, and sci and peritoneal dissemination in metastatic types, whereas no correlation was observed in other factors except between med and a localized type, sci and infiltrating type in gross type. The study of tumorigenicity in nude mice showed remarkable difference between med (86.7%) and sci. (0%). These results indicate that there is definite relationship between the amount of connective tissue and the biological behavior of a gastric cancer.
Connective tissue dysplasia is a systemic process that modifies the clinical picture and course of an acquired pathology. To search additional criteria for differential diagnosis, connective tissue metabolic parameters were studied in patients with infiltrative pulmonary tuberculosis and nosocomial pneumonia. A significant excess of the parameters of free urinary oxyproline and serum glycosaminoglycans was found in patients with infiltrative pulmonary tuberculosis.
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We investigated the incidence of herpes zoster (HZ) and the immunological state to HZ in patients with rheumatoid arthritis (RA) and mixed connective tissue disease (MCTD) in comparison with systemic lupus erythematosus (SLE). HZ occurred in 6 (25%) out of 24 patients with RA and 4 (22%) out of 18 patients with MCTD. One patient had had HZ before the diagnosis of RA. On the other hand, all 4 patients with MCTD had had HZ before the diagnosis of MCTD. The patients with RA and MCTD showed normal or higher antibody titers to varicella zoster virus (VZV) than normal subjects as assayed by both complement fixation technique and neutralization test. However, the antibody levels were not very high compared to those in patients with SLE. On the other hand, only 7 (50%) of 14 patients with RA and 4 (40%) of 10 patients with MCTD showed positive skin reactions to VZV antigen, whereas all 15 normal subjects had positive reactions. Thus, cellular immunity to VZV was thought to be impaired in these diseases. In the patients who were receiving less than 10 mg/day of prednisolone, 7 (64%) of 11 had positive skin reactions in RA patients and 3 (60%) out of 5 patients with MCTD, whereas none (0%) out of 3 patients with RA and 1 (20%) out of 5 patients with MCTD who were receiving 10 mg/day or more prednisolone showed positive skin reactions. These results suggest that the high incidence of HZ in patients with RA and MCTD is probably due to an impaired cellular immunity as in the case of SLE.
Our objective was to investigate longitudinally, antibodies against central nervous tissue (anti-CNS) derived from bovine brain and gangliosides GM 1, GD1a, GD1b, and GT1b in 91 patients with connective tissue diseases (systemic lupus erythematosus, n = 38; mixed connective tissue disease, n = 16; primary Sjogren's syndrome, n = 7; progressive systemic sclerosis, n= 13; polymyositis/dermatomyositis, n=4; overlap syndrome, n = 5; undifferentiated connective tissue disease, n = 8). Anti-CNS and anti-ganglioside antibodies, measured by enzyme-linked immunosorbent assay, were found in 73% and 63% of patients, respectively. Anti-CNS positive sera were also reactive in Western blotting in 74% of cases and recognized up to 14 different polypeptides from 29 to 130 kDa. Anti-CNS and anti-ganglioside antibodies reflected only in a limited extent the disease activity. In 27 of 58 patients, anti-CNS antibodies remained positive independently of disease activity and antibody levels did not correlate with the phases of exacerbations. A total of 36 of 60 anti-CNS-positive patients, in contrast to two of 22 anti-CNS-negative patients, had major neuropsychiatric manifestations (P < 0.001). Anti-ganglioside antibodies were not significantly associated with neuropsychiatric manifestations. In conclusion, our longitudinal data suggest that anti-CNS antibodies may be an important marker for the diagnosis of cerebral involvement in connective tissue diseases, but the pathogenic role of these autoantibodies remains to be determined.
Spondylarthropathies (SpA) and connective tissue diseases (CTD) are clinically distinct entities which, at first glance, seem to have little in common. However, a link between SpA and CTD has recently been suggested by a study in which a higher prevalence of Sjögren's syndrome (SS) and sicca symptoms was reported in patients with ankylosing spondylitis (AS) and undifferentiated SpA (1). Another link between SpA and CTD is a possible side effect of a DMARD widely used to treat SpA: sulfasalazine (SAS). SAS was reported to induce antinuclear antibodies (ANA) and systemic lupus erythematosus (SLE)-like syndromes such as drug-induced lupus. This report describes a 54-year-old white male, HLA B27-positive AS patient with some syndesmophytes who, after 15 years of disease, developed SS with salivary gland involvement, Raynaud's syndrome and anti-Ro antibodies. Then, 20 years after the onset of AS, he became acutely ill, suffering severe myositis and myocarditis along with swollen hands and highly elevated autoantibody titers recognizing UIRNP; his condition was interpreted as mixed connective tissue disease (MCTD). The patient had been treated with SAS and azathioprine (AZA) alone several times during the last years because he had not tolerated other DMARDs. A combination of both drugs had been prescribed 3 weeks before a severe flair because of progredient high disease activity with painful peripheral arthritis of the MCP and PIP joints which, however, had not shown radiographic erosions. We describe the rare development of MCTD in an AS patient and report, for the first time, the onset of MCTD potentially triggered by sulfasalazine.
Connective tissue diseases have been described in patients who have had silicone augmentation mammoplasty. Several possible mechanisms of pathogenesis are postulated. Although otherwise indistinguishable from other connective tissue disease, these patients may experience improvement or remission following implant removal. Current data suggest that the risk of disease after silicone breast augmentation is less than one percent. A large well-designed epidemiologic study will be needed to confirm this association.
CTAP-I from lymphocytes and CTAP-III from platelets markedly stimulated 35SO4= incorporation into chondroitin 4/6 sulfate and dermatan sulfate synthesized by human synovial, dermal, and cartilage connective tissue cells in vitro. These agonists promoted synthesis of the GAG carbon chain as well as sulfate incorporation. Both RNA and protein synthesis were required for these mediators to be effective in stimulating synthesis of connective tissue matrix components. A major part of the capacity of normal serum to stimulate sulfate incorporation into GAG's may reside in CTAP-III.
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Connective tissue consists of collagen, elastic fibers and ground substances produced by fibrocytes. These cells are usually spindle-shaped with slender nuclei and bipolar cytoplasmic extensions. Apart from labeling for vimentin and variable reactivity for factor XIIIa and CD34, fibrocytes are immunonegative. Electron microscopy reveals prominent endoplasmic reticulum, but is otherwise indistinct. Lesions with fibrocytic differentiation can be divided into five categories: scars, keloids, dermatofibromas, nodular fasciitis, and superficial fibromatoses are inflammatory lesions. Thereby, dermatofibromas and their subcutaneous/deep soft tissue counterpart nodular fasciitis can present with a wide variety of clinicopathologic variants which may be misinterpreted as malignancies. Prurigo nodularis, chondrodermatitis nodularis helicis, acanthoma fissuratum, and knuckle pads are hyperplasias; fibroma molle, fibrous papules, connective tissue nevi, and elastofibroma are hamartomas; and fibroma of tendon sheath, pleomorphic fibroma, and giant cell tumor of tendon sheath are benign neoplasms. Deep fibromatoses, dermatofibrosarcoma protuberans, giant cell fibroblastoma, giant cell angiofibroma, hyalinizing spindle cell tumor with giant rosettes, solitary fibrous tumor, myxofibrosarcoma, low-grade fibromyxoid sarcoma, acral myxoinflammatory fibroblastic sarcoma, and classical fibrosarcoma, are malignant neoplasms, that is fibrosarcomas of variable malignant potential. Lesions dominated by myocytes/ myofibroblasts, e.g. cutaneous myofibroma/infantile myofibromatosis, or by macrophages, e.g. xanthogranulomas, are not part of this chapter.
Connective tissue diseases affect frequently women during the childbearing period. As fertility is not considerably reduced in these patients, monitoring and treatment of a pregnant patient is a complex clinical setting that requires an intensive cooperation between gynecologists, rheumatologists and pediatricians. In this article, a 4-point-program for the clinical management of these patients is presented that addresses specifically the problems inherent with the identification of patients with connective tissue diseases, preconceptional diagnostics as well as monitoring and treatment during pregnancy and the postpartal period. Clinical aspects that are intensively discussed include immunosuppressive therapy during pregnancy, the management of antiphospholipid antibody-dependent problems and the prophylaxis and treatment options for congenital heart block.
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Connective tissue cells of liver parenchyma are known as hepatic myofibroblasts and lipocytes (fat-storing cells, Ito-cells). They are considered to belong to a single cell lineage, that may switch between these two phenotypes. We have studied cellular and molecular parameters and controls of this switch in the murine GRX cell line, established from liver fibro-granulomatous lesions induced by schistosomal infection. Accumulation of neutral lipids (triacylglycerols, monoalkyl-diacylglycerol, cholesterol) was monitored. It was dependent upon induction with indomethacin. Insulin alone did not induce lipid accumulation in GRX cells, but in cells induced by indomethacin it increased the quantity of stored lipids. We propose that hepatic lipocytes are not cells directly involved in energy storage, but that they represent a particular cell population specialized in storage and in controls of the homoeostasis of lipid-soluble substances at the systemic level.
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