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Results for “Scleroderma, Diffuse”

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At least 613 records · Page 34Linked to original sources
PubMed2004

Increased expression levels of integrin alphavbeta5 on scleroderma fibroblasts.

Integrin alphavbeta5 is a receptor for vitronectin, a plasma glycoprotein that is also distributed in extracellular matrix of various tissues. Matrix-bound vitronectin has the potential to stabilize the active form of plasminogen activator inhibitor-1, resulting in the inhibition of the plasmin-mediated pericellular proteolytic cascade. In this study, we compared the levels of alphavbeta5 and matrix-bound vitronectin between normal and scleroderma fibroblasts and investigated the association with fibrosis. We demonstrated that alphavbeta5 was up-regulated on scleroderma fibroblasts. The up-regulated alphavbeta5 contributed to the increase in vitronectin-binding ability in scleroderma fibroblasts, which led to the vitronectin-dependent activation of plasminogen activator inhibitor-1. In immunohistochemistry, the alphav and beta5 subunits were stained strongly on scleroderma fibroblasts and the amount of vitronectin was increased in the pericellular matrix of those cells. The transient overexpression of alphavbeta5 on normal fibroblasts enhanced the human alpha2(I) collagen promoter activity through Sp-1 and Smad3 as well as the vitronectin-dependent plasminogen activator inhibitor-1 activity. This effect on the promoter activity was also observed in the absence of vitronectin and completely disappeared in the presence of anti-alphavbeta5 antibody. These results indicate that the up-regulated alphavbeta5 may contribute to the phenotypical alteration of scleroderma fibroblasts, while at the same time suppressing the plasmin-mediated pericellular proteolytic cascade.

Blotting, Northern↗
PubMed2003

Scleroderma renal crisis.

Explore the source record for details and available documents.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

Cytokine regulation of pulmonary fibrosis in scleroderma.

Pulmonary fibrosis occurs in up to 70% of scleroderma patients and progresses to cause severe restrictive lung disease in about 15% of patients. The mechanisms that cause pulmonary fibrosis in scleroderma remain incompletely understood. Increased amounts of mRNA or protein for multiple profibrotic cytokines and chemokines have been identified in lung tissue or broncholveolar lavage samples from scleroderma patients, when compared to healthy controls. These cytokines include transforming growth factor (TGF)-beta, connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF), oncostatin M (OSM), monocyte chemotactic factor-1 and pulmonary and activation-regulated chemokine (PARC). Potential cellular sources of these profibrotic cytokines and chemokines in scleroderma lung disease include alternatively activated macrophages, activated CD8+ T cells, eosinophils, mast cells, epithelial cells and fibroblasts themselves. This review summarizes the literature on involvement of cytokines and chemokines in the development of pulmonary fibrosis in scleroderma.

Adult↗
PubMedDate not supplied

A pediatric case of sclerodermatous chronic graft-versus-host disease.

We report a rare case of sclerodermatous chronic graft-versus-host disease (GVHD) in a 6-year-old boy that occurred after bone marrow transplantation for his aplastic anemia. The clinical manifestation and histopathologic findings were typical of scleroderma. Although various kinds of treatment have been tried for scleroderma, no established therapy exists. Furthermore, treating this disease is even more difficult in children. In the future, clarification of the pathogenesis of chronic GVHD and establishment of therapy will be necessary.

Anemia, Aplastic↗
PubMed2003

Treatment of scleromyxoedema with hydroxychloroquine.

BACKGROUND: Scleromyxoedema is a rare disease of unknown aetiology that is characterized by deposition of mucin and sclerotic induration of the skin; it is associated with paraproteinaemia. Patients suffer from progressive disability due to immobilization and cosmetic disfigurement. Treatment of scleromyxoedema is a therapeutic challenge. The antimalarial hydroxychloroquine has a rapid and reliable effect in reticular erythematous mucinosis. PATIENTS AND METHODS: Four consecutive patients (two women, two men; median age: 50 years) with scleromyxoedema, three of them with IgG lambda paraprotein, were treated with hydroxychloroquine. Treatment was initiated with 600 mg p.o. for 10 days, followed by 400 mg for at least 4 weeks, and 200 mg thereafter. RESULTS: Complete remission of skin manifestations was achieved in one patient, whereas three patients achieved a partial remission of 61+, 5 and 25 months' duration. Notably, three patients felt increased mobility and reduced firmness of skin during the first week of treatment, which was reflected in a rapid reduction in dermal thickness. In one patient, dysphagia was reverted as evidenced by normalization of oesophageal clearance. Paraproteinaemia was not influenced at all. Side effects included one case of electroretinogram abnormalities after 19 months of therapy and one case of leucopenia after 3 months. CONCLUSION: Hydroxychloroquine is an effective form of therapy for scleromyxoedema, leading to rapid and prolonged alleviation of symptoms.

Adult↗
PubMed2005

Late recurrence of scleroderma renal crisis in a renal transplant recipient despite angiotensin II blockade.

Scleroderma renal crisis is the most severe renal manifestation of scleroderma and has been reported to recur rarely early after renal transplantation. Angiotensin II blockade is critical in preventing and treating scleroderma renal crisis, but some concern exists as to whether angiotensin II receptor blockers are clinically equivalent to angiotensin-converting enzyme inhibitors. The current case indicates that late recurrences of scleroderma renal crisis are possible in renal transplant recipients and that angiotensin-converting enzyme inhibitors, rather than angiotensin II receptor blockers, may be the superior drugs for such patients.

Adult↗
PubMed2005

[Progressive systemic sclerosis and pregnancy].

Progressive systemic sclerosis is a connective tissue disease with inflammation and fibrosis. Pregnant women with progressive systemic sclerosis have an increased risk for preterm births and probably for small-for-date babies. We report the case of a 28-year-old II G O P suffering from progressive systemic sclerosis with severe pulmonary fibrosis and affection of the oesophagus. She was admitted to hospital at 32 weeks of gestation with premature labour and cervical incompetence. At 34 weeks of gestation she was delivered by Caesarean section with spinal anaesthesia because of foetal growth arrest and decreased pulmonary function. The operation and the postoperative course were without any complications. Pregnant women with progressive systemic sclerosis have an increased risk for renal and pulmonary complications (hypertension, hypoxia). Therefore careful interdisciplinary obstetric monitoring is very important.

Adult↗
PubMed2003

Transcriptional inhibition of type I collagen gene expression in scleroderma fibroblasts by the antineoplastic drug ecteinascidin 743.

We previously showed that COL1A1 expression is up-regulated at the transcriptional level in systemic sclerosis (SSc) fibroblasts and that the CCAAT-binding factor (CBF) is involved in this increased expression. Ecteinascidin 743 (ET-743) is a chemotherapeutic agent that binds with sequence specificity to the minor groove of DNA and inhibits CBF-mediated transcriptional activation of numerous genes. Therefore, we examined the effects of ET-743 on the increased COL1A1 expression in SSc fibroblasts. The drug caused a potent and dose-dependent inhibition of type I collagen biosynthesis, which reached 70-90% at 700 pM without affecting cell viability. The same drug concentration caused 60-80% reduction in COL1A1 mRNA levels. The stability of the corresponding transcripts was not affected. In vitro nuclear transcription assays demonstrated a 54% down-regulation of COL1A1 transcription. Transient transfections with COL1A1 promoter constructs containing the specific CBF binding sequence into SSc cells previously treated with 700 pM ET-743 failed to show an effect on COL1A1 promoter activity. Furthermore, ET-743 did not affect the binding of CBF or Sp1 transcription factors to their cognate COL1A1 elements. However, treatment with 700 pM ET-743 of stably transfected NIH 3T3 cells expressing a human type II procollagen gene under the control of the human COL1A1 promoter caused a greater than 50% reduction in the production of type II procollagen and a similar decrease in the corresponding type II procollagen transcripts. These results indicate that ET-743 is a potent inhibitor of COL1A1 transcription. However, this effect cannot be explained by a direct effect on CBF binding to the COL1A1 promoter. Although the exact mechanisms responsible for the transcriptional inhibition of COL1A1 by ET-743 are not apparent, our observations suggest that the drug may be an effective agent to decrease collagen overproduction in SSc and other fibrotic diseases.

3T3 Cells↗
PubMed2006

The role of IL-4 and IL-12 in the regulation of collagen synthesis by fibroblasts.

Chronic sclerodermifomic graft versus host disease is a rare but important complication of allogeneic hematopoietic stem cell transplantation that especially occurs in patients who are treated with donor lymphocyte infusions for relapse of a malignant disease. Today most knowledge about the pathogenesis of chronic Graft-versus-Host Disease is based on mice models. In this report we describe the development of an allogeneic in vitro model that allows studying the pathogenesis of chronic sclerodermifomic Graft-versus-Host Disease in the human setting. We report that priming of mononuclear cells in the presence of allogeneic fibroblasts and Interleukin (IL)-4 induces fibroblast collagen synthesis, whereas priming in the presence of IL-12 suppresses collagen synthesis during subsequent coculture of primed mononuclear cells with allogeneic fibroblasts. Since IL-12 is also known to mediate anti-tumor effects by stimulation of Natural Killer cell and Lymphokine Activated Killer cell activity, these findings indicate that treatment of patients with IL-12 or pretreatment of donor lymphocytes with IL-12 might strengthen a graft versus leukemia effect and at the same time decrease the risk of chronic sclerodermifomic Graft-versus-Host Disease development.

Animals↗
PubMed2006

Intracellular Th1/Th2 balance of pulmonary CD4(+) T cells in patients with active interstitial pneumonia evaluated by serum KL-6.

The balance between CD4(+) T helper (Th1) lymphocytes producing interferon-gamma or Interleukin-4 (Th2) in the lungs may vary among diseases and during the progression of interstitial pneumonia (IP). Both idiopathic pulmonary fibrosis (IPF) and collagen vascular diseases (CVD) are associated with IP, but the clinical course and the response to treatment are different. Since Th1 or Th2 modulating drugs have been proven to alter the lymphocyte balance in vitro, it is important to elucidate the Th1/Th2 profile in patients with active IP. Bronchoalveolar lavage (BAL) was performed in patients who had IPF (n = 12) or CVD (n = 12) with IP, as well as in patients who had bronchoectasis and bronchopneumonia (n = 12). The CVD patients had rheumatoid arthritis (n = 6), Sjogren's syndrome (n = 2), dermatomyositis (n = 1), progressive systemic sclerosis (n = 2), and CREST syndrome (n = 1) as the underlying diseases. IP activity was evaluated by measuring serum KL-6, which is a clinically useful indicator for IP. The Th1/ Th2 balance and the CD4(+)/CD8(+) ratio were determined for lymphocytes obtained from BAL by flow cytometric analysis. In IPF patients, the CD4(+)/CD8(+) ratio was lower than in CVD patients. IPF patients showed Th2 dominance and CVD patients showed Th1 dominance when IP was active as evaluated by the serum KL-6 level. These data indicated that the Th1/Th2 balance of CD4(+) T cells in the BAL differs between active IPF and CVD, even though KL-6 is elevated in both diseases. Therefore, the Th1/Th2 profile should be investigated to determine the use of Th1/Th2 modulator therapy for active IP with elevation of KL-6.

Aged↗
PubMedDate not supplied

New ELISA kits using C3 binding glycoprotein from Cuscuta europea detect mainly IgM CIC in rheumatoid arthritis and progressive systemic sclerosis, but not in systemic lupus erythematosus.

Elevated levels of circulating immune complexes (CIC), containing IgG, IgM or IgA antibodies were detected in the sera of patients with autoimmune diseases. This might indicate a different biological meaning of the three isotypes of immunoglobulin (Ig) in the CIC. Each CIC assay detected only certain classes and subclasses of Ig in CIC material or fixed complement protein. In this study, a new method based on C3binding glycoprotein named CIF-ELISA and a well-known method ANTI-C3 ELISA, were used for quantitative assessment of IgM-CIC, IgG-CIC and IgA-CIC levels in human sera. A modified CIF-ELISA and ANTI-C3 ELISA for simultaneous detection of CIC, containing IgG, IgM and IgA, (stCIC), were also performed. The assays were evaluated on the same specially prepared samples: 55 normal sera, 99 sera from rheumatoid arthritis (RA), 88 sera from systemic lupus erythematosus (SLE), and 27 sera from progressive systemic sclerosis (PSS). We found that the sensitivity of the tests used varied depending on the diseases studied. CIF-ELISA displayed higher sensitivity of IgM-CIC when compared to ANTI-C3 ELISA in RA patients (40.0 and 20.95%, respectively) and PSS (44.43 and 37.04%, respectively). Results for the sensitivity of IgA-CIC were in adverse direction in the RA group (14.28 and 19.05%) and PSS (14.81 and 25.93%) by both methods. It was also established that the concordance of IgM-CIC positives by both methods was 48.84% in RA and 46.67% in PSS, while in SLE it was 18.78%. These results are most probably due to the different assay abilities to detect antibody isotype of the CIC material and help to explain what specific role each Ig isotype in CIC has in the course of the disease.

Antigen-Antibody Complex↗
PubMed2003

Stem-cell transplantation for autoimmune diseases.

The use of intensive immunosuppressive treatment coupled with BM stem-cell transplantation (SCT) to treat human autoimmune diseases (AID) follows anecdotal observations of responses of AID to allogeneic SCT and an extensive background of experience with SCT in animals with AID. In the last decade, numerous clinical trials have been initiated to explore a potential benefit of (mainly autologous) SCT in advanced and debilitating cases of rheumatoid arthritis, scleroderma, systemic lupus erythematosis and multiple sclerosis. In this review the etiology of AID and the experimental basis of SCT is presented, together with recent clinical results of SCT for AID. While much has been learned about the risks and benefits of SCT in AID, the underlying mechanisms regulating remission and relapse of AID after treatment remain largely unknown.

Autoimmune Diseases↗
PubMed1981

Long-term follow-up of the combined fundic patch fundoplication for treatment of longitudinal peptic strictures of the esophagus.

Optimum treatment of patients with esophageal strictures requires of the operating surgeon a wide repertoire of procedures suited to the individual circumstance. The Thal-Nissen procedure should be used in the patient with a longitudinal transmural stricture which cannot be easily dilated. When used in this setting, it widens the distal esophagus with a patch of well vascularized fundus and provides extremely effective protection against gastroesophageal reflux. Sixty-eight patients at the University of Florida underwent combined Thal-Nissen procedures for longitudinal peptic strictures. Operative mortality rate was 4%. The average length of follow-up was 68 months. Fifty-seven of 68 patients had an acceptable result (84%). Four per cent had an early recurrence of their stricture, while an additional 4% had late recurrence of their strictures, after an initially good response period of from two to 11 years. Four of the six patients with poor results had either achalasia, scleroderma, or diffuse esophageal spasm. The combined Thal-Nissen procedure represents the optimum therapy for the patient with an undilatable transmural stricture of the esophagus. When used in this setting, satisfactory results will be achieved in a large majority of patients with an extremely low operative mortality rate. Colonic or jejunal interposition should be reserved for those patients who either fail to respond to a combined Thal-Nissen procedure or who demonstrate sufficiently disordered peristalsis to render the esophagus an unsatisfactory conduit for the passage of food.

Adolescent↗
PubMed2000

Diffuse and limited cutaneous systemic scleroderma.

Juvenile systemic scleroderma (jSSc) is a rare disease. Based on the first large data collection on this patient group, the disease course was demonstrated to differ from that in adults. The concept of persistence of maternal cells in patients with SSc remains pathogenetically fascinating, as does the resemblance with graft-versus-host-disease. In view of new therapeutic options, controlled trials have not established a gold standard for treatment, but autologous bone marrow transplantation may be considered a rescue therapy for selected patients. Palliative therapies have also improved markedly in recent years. The first controlled trials for patients with jSSc are being proposed.

Adult↗