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Geetha Sugumaran

Publications and source records attributed to Geetha Sugumaran.

4 recordsLinked to original sources
PubMed2003

Hyaluronan is not elevated in urine or serum in Hutchinson-Gilford Progeria Syndrome.

Elevations in urinary hyaluronan have been used as the principal laboratory indicator for diagnosis of Hutchinson-Gilford Progeria Syndrome (HGPS). Previous reports have provided evidence suggesting that children with HGPS have altered hyaluronan metabolism as indicated by a mean 17-fold increase in urinary hyaluronan over normal values. In addition, adults with Werner's syndrome have elevated urinary hyaluronan and even more prominent elevations in serum hyaluronan over age-matched controls. It is not known whether serum hyaluronan is elevated or whether serum hyaluronan levels correlate with urinary hyaluronan levels in children with HGPS. In a large cohort of 19 HGPS patients, we sought to confirm elevations in urinary hyaluronan concentration, to establish whether serum hyaluronan is elevated, to measure the size of urinary hyaluronan, and to determine whether serum or urine hyaluronidase levels are altered. We have analyzed urinary and serum hyaluronan levels in patients with HGPS and control patients (1) by using an enzyme-linked immunosorbent assay (ELISA)-like method in which sample hyaluronan in solution and hyaluronan in solid phase compete for a solution of biotinylated hyaluronan-binding protein, and (2) by fluorophore-assisted carbohydrate electrophoresis. The size of urinary hyaluronan was measured by using Sepharose CL-6B size exclusion chromatography. Serum and urinary hyaluronidases were evaluated quantitatively, by using ELISA, and qualitatively, by using a gel detection method. HGPS patients did not show a significant elevation in either urinary or serum hyaluronan. We detected no difference in the size of urinary hyaluronan between HGPS children and age-matched controls. Serum and urinary hyaluronidase levels were not significantly different in normal and HGPS patients. These studies indicate that neither serum nor urinary hyaluronan concentration is a reliable diagnostic or prognostic marker for HGPS and underscore a difference between adult and childhood progerias.

Chromatography, High Pressure Liquid↗
PubMed2002

Biosynthesis of chondroitin/dermatan sulfate.

Chondroitin sulfate and dermatan sulfate are synthesized as galactosaminoglycan polymers containing N-acetylgalactosmine alternating with glucuronic acid. The sugar residues are sulfated to varying degrees and positions depending upon the tissue sources and varying conditions of formation. Epimerization of any of the glucuronic acid residues to iduronic acid at the polymer level constitutes the formation of dermatan sulfate. Chondroitin/dermatan glycosaminoglycans are covalently attached by a common tetrasaccharide sequence to the serine residues of core proteins while they are adherent to the inner surface of endoplasmic reticulum/Golgi vesicles. Addition of the first sugar residue, xylose, to core proteins begins in the endoplasmic reticulum, followed by the addition of two galactose residues by two distinct glycosyl transferases in the early cis/medial regions of the Golgi. The linkage tetrasaccharide is completed in the medial/trans Golgi by the addition of the first glucuronic acid residue, followed by transfer of N-acetylgalactosamine to initiate the formation of a galactosaminoglycan rather than a glucosaminoglycan. This specific N-acetylgalactosaminyl transferase is different from the chondroitin synthase involved in generation of the repeating disaccharide units to form the chondroitin polymer. Sulfation of the chondroitin polymer by specific sulfotransferases occurs as the polymer is being formed. All the enzymes in the pathway for synthesis have been cloned, with the exception of the glucuronyl to iduronyl epimerase involved in the formation of dermatan residues.

Animals↗
PubMed2002

Proteoglycans synthesized by canine intervertebral disc cells grown in a type I collagen-glycosaminoglycan matrix.

The objective of this study was to determine the characteristics of proteoglycans synthesized by canine annulus fibrosus cells expanded in number in monolayer culture through passage 4 and subsequently grown in a type I collagen-glycosaminoglycan matrix to be employed for tissue engineering. Newly synthesized [35S]sulfate-labeled proteoglycans were analyzed by gel chromatography, including sequential digestion with enzymes and nitrous acid. After 1 week in culture, the percentage of cell-associated, aggregated proteoglycans synthesized in type I collagen-glycosaminoglycan matrices was 52% compared with 38% by the cells in monolayer. The percentage of aggregated proteoglycan in each group increased only slightly with the addition of exogenous hyaluronic acid, but remained significantly different from each other. There were at least three different hydrodynamic sizes of proteoglycans both in the collagen-glycosaminoglycan matrix and in monolayer; the average size was larger in the collagen matrices and the glycosaminoglycan chains were longer. The proteoglycans contained chondroitin sulfate, dermatan sulfate, heparan sulfate, and keratan sulfate. The results provide a foundation for future investigations of collagen-glycosaminoglycan matrices for intervertebral disc tissue engineering.

Animals↗