epidermal-growth-factor and Connective-Tissue-Diseases

Saliva plays a role in mucosal protection and ulcer healing.. : To study whether decreased salivary production leads to peptic ulcer disease in connective tissue disease patients associated with xerostomia.. Two hundred and two connective tissue disease patients (90 with xerostomia and 112 without xerostomia) were enrolled. Their demographic data and use of medications were recorded. Peptic ulcer disease was confirmed by endoscopy. The stimulated salivary output and secretory epidermal growth factor level were measured.. Compared with non-xerostomic counterparts, xerostomic patients manifested a higher occurrence of peptic ulcer disease (31% vs. 12%, P = 0.001), lower stimulated salivary output (9.3 +/- 4.1 vs. 22.9 +/- 5.9 mL/15 min, P < 0.001) and lower stimulated salivary epidermal growth factor output (1.40 +/- 0.77 vs. 3.00 +/- 0.96 ng/min, P < 0.001). Multivariate analysis disclosed that an older age (> or = 60 years) (odds ratio, 4.71; P < 0.001), xerostomia with stimulated salivary output of < or =1 mL/min (odds ratio, 7.54; P = 0.014) and the use of non-steroidal anti-inflammatory drugs (odds ratio, 5.76; P = 0.031) were the risk factors leading to peptic ulcer disease. In addition, xerostomic connective tissue disease patients receiving non-steroidal anti-inflammatory drugs manifested an extremely high risk of development of peptic ulcer disease (odds ratio, 19.78; P < 0.001).. Ageing, the use of non-steroidal anti-inflammatory drugs and poor salivary function are potential risk factors for the development of peptic ulcer disease in patients with connective tissue disease. If these xerostomic subjects consume non-steroidal anti-inflammatory drugs, they will encounter an extremely high peptic ulcer disease risk.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Case-Control Studies; Connective Tissue Diseases; Dyspepsia; Epidermal Growth Factor; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Peptic Ulcer; Regression Analysis; Risk Factors; Xerostomia

The nuclear magnetic resonance structure of a covalently linked pair of calcium-binding (cb) epidermal growth factor-like (EGF) domains from human fibrillin-1, the protein defective in the Marfan syndrome, is described. The two domains are in a rigid, rod-like arrangement, stabilized by interdomain calcium binding and hydrophobic interactions. We propose a model for the arrangement of fibrillin monomers in microfibrils that reconciles structural and antibody binding data, and we describe a set of disease-causing mutations that provide the first clues to the specificity of cbEFG interactions. The residues involved in stabilizing the domain linkage are highly conserved in fibrillin, fibulin, thrombomodulin, and the low density lipoprotein receptor. We propose that the relative orientation of tandem cbEGF domains in these proteins is similar, but that in others, including Notch, pairs adopt a completely different conformation.

Topics: Calcium-Binding Proteins; Connective Tissue Diseases; Epidermal Growth Factor; Humans; Image Processing, Computer-Assisted; Marfan Syndrome; Microfilament Proteins; Molecular Sequence Data; Mutation; Protein Conformation; Protein Structure, Tertiary; Sequence Homology, Amino Acid

The circulating levels of hyaluronate were determined in 36 patients with scleroderma and in 36 control subjects matched for age and sex. The mean serum hyaluronate concentration in patients with progressive systemic sclerosis (n = 25) was 131 +/- 67 (SD) microgram/l and significantly greater (p less than 0.001) than that of the controls (mean level 49 +/- 21 (SD) microgram/l). Hyaluronate levels in patients with localised scleroderma (n = 4) were 141 +/- 47 (SEM) microgram/l and in patients with scleroderma-associated overlap syndromes (n = 7) 202 +/- 54 (SEM) microgram/l. The increase in serum hyaluronate probably reflected an enhanced synthesis or outflow of hyaluronate from the connective tissue, or both; it could not be explained by affection of the liver, which is the catabolic site of hyaluronate. The hyaluronate values were not related to certain serological indicators of inflammatory activity or to the extent of the skin lesions or the severity of internal organ manifestations. A positive correlation was noted between circulating platelet counts and hyaluronate levels (p less than 0.001). Plasma beta-thromboglobulin was measured in 15 of the patients with systemic sclerosis and found to correlate positively with platelet counts. Raised levels of beta-thromboglobulin were associated with the highest hyaluronate values. Platelet-derived growth factor, which stimulates connective tissue cells and is stored in the alpha-granules of platelets together with beta-thromboglobulin, was shown to enhance hyaluronate synthesis in fibroblast cultures. The results suggest an involvement in scleroderma of connective tissue activating substances released from platelets.

Topics: Cells, Cultured; Connective Tissue Diseases; Epidermal Growth Factor; Fibroblasts; Humans; Hyaluronic Acid; Middle Aged; Platelet Count; Platelet-Derived Growth Factor; Scleroderma, Systemic

Previously, we found that, at high cell density, human skin fibroblasts produce a higher proportion of type III to type I collagen. Treatment of sparse cultures with prostaglandin E2 also increases this ratio, while treatment of dense cultures with epidermal growth factor reduces it. Similar changes were observed using some strains of fibroblasts from patients with the Ehlers-Danlos syndrome type IV and osteogenesis imperfecta. Studies on the extent of intracellular degradation suggest that the changes observed could be caused in part by changes in the breakdown of collagen inside the cell with preferential loss of type I collagen and/or changes in synthesis of the two proteins.

Topics: Cell Adhesion; Cells, Cultured; Collagen; Connective Tissue Diseases; Cyclic AMP; Epidermal Growth Factor; Humans; Prostaglandins E; Skin