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Results for “Scleroderma, Diffuse”

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At least 649 records · Page 36Linked to original sources
PubMed2004

Phosphatidylinositol 3-kinase is involved in alpha2(I) collagen gene expression in normal and scleroderma fibroblasts.

TGF-beta is implicated in the pathogenesis of fibrotic disorders. It has been shown that Smad3 promotes the human alpha2(I) collagen (COL1A2) gene expression by TGF-beta1 in human dermal fibroblasts. Here, we investigated the role of phosphatidylinositol 3-kinase (PI3K) in the COL1A2 gene expression in normal and scleroderma fibroblasts. In normal fibroblasts, the PI3K inhibitor, LY294002, significantly decreased the basal and the TGF-beta1-induced increased stability of COL1A2 mRNA. The TGF-beta1-induced COL1A2 promoter activity, but not the basal activity, was significantly attenuated by LY294002 or the dominant negative mutant of p85 subunit of PI3K, while the constitutive active mutant of p110 subunit of PI3K did not affect the basal or the TGF-beta1-induced COL1A2 promoter activity. LY294002 significantly decreased the phosphorylation of Smad3 induced by TGF-beta1. Furthermore, the transient overexpression of 2xFYVE, which induces the mislocalization of FYVE domain proteins, decreased the TGF-beta1-induced Smad3 phosphorylation to a similar extent to LY294002. In scleroderma fibroblasts, the blockade of PI3K significantly decreased the mRNA stability and the promoter activity of the COL1A2 gene. Furthermore, LY294002 and the transient overexpression of 2xFYVE completely diminished the constitutive phosphorylation of Smad3. These results indicate that 1) the basal activity of PI3K is necessary for the COL1A2 mRNA stabilization in normal and scleroderma fibroblasts, 2) there is an unidentified FYVE domain protein specifically interacting with Smad3, and 3) the basal activity of PI3K and the FYVE domain protein are indispensable for the efficient TGF-beta/Smad3 signaling in normal fibroblasts and for the establishment of the constitutive activation of TGF-beta/Smad3 signaling in scleroderma fibroblasts.

Cells, Cultured↗
PubMedDate not supplied

Apoptosis and necrosis increase antigenicity of proteins recognized by antinuclear antibodies.

OBJECTIVE: Present study addresses the issue whether apoptosis and necrosis increases the antigenicity of proteins recognized by antinuclear antibodies. MATERIAL AND METHODS: HEp-2 cells were cultured in standard conditions; apoptosis was induced by camptothecin and necrosis by mercuric chloride. Protein antigenicity of cell extracts was tested onto nitrocellulose membranes and probed with positive or negative sera for antinuclear antibodies by a luminescent-dot-ELISA system. RESULTS: Apoptotic changes in HEp-2 cells appeared by 24 hours of camptothecin exposure, meanwhile the necrotic features become visible earlier. Luminescence was significantly superior in ANA positive sera than in ANA negative controls. Antinuclear antibody sera recognized better the antigens from the apoptotic and necrotic cells than controls without chemical treatments. CONCLUSIONS: Apoptosis and necrosis increase the ANA binding by better availability of intracellular antigens, or by disclosing cryptic epitopes.

Antibodies, Antinuclear↗
PubMed2000

[Severe isolated pulmonary hypertension as main manifestation of Crest syndrome].

Interstitial pulmonary fibrosis is the leading cause of secondary pulmonary hypertension in systemic sclerosis, and it occurs in either limited or diffuse cutaneous scleroderma subset. Isolated pulmonary hypertension, without pulmonary disease, occurs primarily in patients with limited cutaneous scleroderma (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia [CREST] variant) although it is an unusual feature in this subset, with a worse prognosis in the short term. We present a previously undiagnosed patient with the CREST syndrome, with severe isolated pulmonary hypertension and secondary respiratory failure as major feature of its connective tissue disease. Clinical, prognostic and therapeutical aspects are commented.

Aged↗
PubMed2003

The pattern of esophageal manometry in progressive systemic sclerosis.

OBJECTIVE: The purpose of this paper is to study the esophageal motility pattern and the frequency of acid reflux in patients diagnosed to have progressive systemic sclerosis and compare the results to that of normal controls. METHODS: All consecutive patients diagnosed to have progressive systemic sclerosis between 1417-1419 (Hijra year) at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia were included (Group I). History of heartburn, dysphagia and regurgitation was reviewed. Drugs that might suppress acid or alter motility were discontinued 2 weeks before inclusion. The results were compared to that of 21 symptomatic controls of similar age and sexes that were seen at the same period (Group II). Esophageal manometry and upper gastrointestinal endoscopy were performed in all patients. Ambulatory 24 hour-pH monitoring was carried out in 6 patients of group 1 and 20 patients of group II. RESULTS: Thirteen progressive systemic sclerosis patients (12 females) mean age was 38.7 years and 21 (19 females) mean age was 34.8 years were included. The symptom scores, lower esophageal sphincter pressure, esophageal contractions amplitude were significantly worse in patients compared to control, dysphagia was mostly due to aperistalsis. All progressive systemic sclerosis patients showed the typical esophageal manometry pattern of lower esophageal sphincter pressure and diminished amplitude with aperistalsis. Gastroesophageal reflux was detected in 83% of patients with progressive systemic sclerosis. Moreover, all 24-hour pH monitoring variables were significantly worse in group I. CONCLUSION: Patients with progressive systemic sclerosis usually present with heartburn, dysphagia and regurgitation. Esophageal manometry typically shows lower pressure and aperistalsis. Gastroesophageal reflux is frequent.

Adult↗
PubMedDate not supplied

[What is your diagnosis? Hypochromic microcytic anemia with Evans syndrome or autoimmune thrombocytopenic purpura?].

We report a case of Evans syndrome associated with scleroderma in a 50-year-old woman admitted to the department of internal medicine of Yalgado Ouedraogo National Teaching Hospital in Burkina Faso. The interest of this case lies in on its mode of revelation: chronic bleeding that led to hypochromic microcytic anemia. The indirect antiglobulin test was positive. Corticosteroid treatment has been successful. Nonetheless, because autoimmune cytopenia may indicate underlying disorders, particularly lymphoid tissue malignancies, rigorous monitoring of this patient is essential.

Adrenal Cortex Hormones↗
PubMed2005

Kidney crisis in systemic sclerosis.

Renal crisis in systemic sclerosis occurs in the group of patients with rapid and aggressive course of the disease, often after several years of the ailment and with the diffuse form. Scleroderma renal crisis (SRC) is most frequently characterized by malignant hypertension, renal insufficiency, and less often by the symptoms of microangiopathic hemolytic anemia. Renal crisis symptoms appear suddenly and are not usually preceded by significant prodromal symptoms. SRC is always life-threatening and requires specific treatment with drugs blocking angiotensin-converting enzyme. Early diagnosis and introducing appropriate treatment give a patient a chance to survive SRC episode and improve his prognosis. SRC is of great importance to clinicians as it still causes high mortality rate. Chronic and subacute renal crisis is connected with a small risk of acute renal failure. However, it gradually leads to a substantial dysfunction of this organ. Thus, a useful examination in the diagnostics of chronic renal crisis is checking the vascular flow in renal cortex and evaluating intrarenal resistance.

Acute Kidney Injury↗
PubMed2005

[Acral scleroderma presenting simultaneously with small-cell bronchial carcinoma: a paraneoplastic disease?].

The possible causal connection between systemic scleroderma and malignant neoplasms is a controversial issue. In the case of dermatomyositis, a malignant tumor is viewed as a possible trigger of the collagen disease; in contrast, scleroderma is suspected of causing tumors because of the long-term tissue fibrosis. A 68-year-old woman presented with acral scleroderma but already had metastatic bronchial carcinoma without evidence for previous pulmonary fibrosis. The rapid spread of the tumor and the sudden appearance of scleroderma suggest that in this case scleroderma could represent a paraneoplastic syndrome. Attention is directed to several growth factors and cytokines. On the one hand they play a part in the neoplastic transformation of the host cells and on the other hand they can change fibroblasts into a profibrotic phenotype and induce fibrosis. Impressive in this case is the fact that acral scleroderma definitely developed after the malignant tumor but before treatment, so that both fibrosis of the lung and side effects of chemotherapy and radiation can be excluded as triggers.

Bronchial Neoplasms↗