Document Detail

Increased sulfatation of orbital glycosaminoglycans in Graves' ophthalmopathy.
MedLine Citation:
PMID:  10199787     Owner:  NLM     Status:  MEDLINE    
Accumulation of interstitial glycosaminoglycans (GAG) in orbital tissue of patients with Graves' ophthalmopathy (GO) leads to edema, increased orbital pressure, and proptosis. In this study, a new, highly sensitive, high performance liquid chromatography method was developed to determine the altered concentration and biochemical composition of different GAG polymers in orbital connective tissue of 27 GO patients and 18 controls. GAG were isolated by tissue homogenization and digestion, followed by sequential enzymatic GAG hydrolysis and high performance liquid chromatographic analysis of the resulting alpha,beta-unsaturated disaccharides. High recovery rates of 78 +/- 6% (mean +/- SE) and a detection limit of 4.0 microg/L (0.01 micromol/L) were obtained. Total tissue GAG amounted to 254 +/- 16 microg/g wet tissue wt in patients and 150 +/- 13 microg/g (P < 0.0001) in controls. Regarding the GAG polymers, marked differences were detected between patients and controls (chondroitin sulfate, 127 +/- 13 vs. 47 +/- 5 microg/g; hyaluronic acid, 56 +/- 5 vs. 34 +/- 4 microg/g; both P < 0.0001; dermatan sulfate, 77 +/- 6 vs. 69 +/- 6 microg/g; P < 0.05). In patients, chondroitin sulfate was the major GAG component (48 +/- 6 vs. 31 +/- 5% of total GAG in controls), whereas dermatan sulfate was dominant in controls (46 +/- 8% vs. 30 +/- 5%). The sulfated disaccharide digestion products were markedly increased (P < 0.0001) in patients, and the ratio of sulfated vs. total disaccharide content was 85 +/- 6% vs. 65 +/- 5% (P < 0.05) in patients and controls, respectively. As accumulation of negatively charged sulfate residues in GAG disaccharides results in enhanced water-binding capacity, beside inflammation and increased volume of the orbital adipose tissue, the altered structure and nature of sulfated GAG units in the orbit may be responsible for the pathogenic changes in Graves' ophthalmopathy.
C Hansen; R Rouhi; G Förster; G J Kahaly
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  84     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  1999 Apr 
Date Detail:
Created Date:  1999-04-21     Completed Date:  1999-04-21     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1409-13     Citation Subset:  AIM; IM    
Department of Endocrinology/Metabolism, Gutenberg-University Hospital, Mainz, Germany.
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MeSH Terms
Aged, 80 and over
Chromatography, High Pressure Liquid
Glycosaminoglycans / metabolism*
Graves Disease / metabolism*
Middle Aged
Orbit / metabolism*
Sulfates / metabolism
Reg. No./Substance:
0/Glycosaminoglycans; 0/Sulfates

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