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Biomedical subjects

N S Vasan

Publications and source records attributed to N S Vasan.

At least 19 recordsLinked to original sources
PubMed1991

A preliminary study of mechanically stress-induced changes in the extracellular matrix of the canine intervertebral disc.

The intervertebral discs of a young (age, 3 years) and an old (age, 8 years) dog were isolated as motion segments and cyclically stressed in physiologic nondestructive axial compression loads. Chemical analysis of the matrix of the annulus fibrosus revealed a shift in proteoglycan molecular size from larger to smaller moieties for the older dog but not for the younger. These preliminary results may indicate an age-related inability of the disc to tolerate cyclic stress.

Aging↗
PubMed1991

A mutation in the pro alpha 2(I) gene (COL1A2) for type I procollagen in Ehlers-Danlos syndrome type VII: evidence suggesting that skipping of exon 6 in RNA splicing may be a common cause of the phenotype.

Fibroblasts from a proband with Ehlers-Danlos syndrome type VII synthesized approximately equal amounts of normal and shortened pro alpha 2(I) chains of type I procollagen. Nuclease S1 probe protection experiments with mRNA demonstrated that the pro alpha 2(I) chains were shortened because of a deletion of most or all of the 54 nucleotides in exon 6, the exon that contains codons for the cleavage site for procollagen N-proteinase. Sequencing of genomic clones revealed a single-base mutation that converted the first nucleotide of intron 6 from G to A. Therefore, the mutation was a change, in the -GT-consensus splice site, that produced efficient exon skipping. Allele-specific oligonucleotide hybridizations demonstrated that the proband's mother, father, and brother did not have the mutation. Therefore, the mutation was a sporadic one. Analysis of potential 5' splice sites in the 5' end of intron 6 indicated that none had favorable values by the two commonly employed techniques for evaluating such sites. The proband is the fourth reported proband with Ehlers-Danlos syndrome VII with a single-base mutation that causes skipping of exon 6 in the splicing of RNA from either the COL1A1 gene or COL1A2 gene. No other mutations in the two type I procollagen genes have been found in the syndrome. Therefore, such mutations may be a common cause of the phenotype. The primers developed should be useful in screening for the same or similar mutations causing the disease.

Alleles↗
PubMed1985

Forskolin- and dibutyryl cyclic AMP-mediated inhibition of chondrogenesis.

The regulatory role of cyclic AMP in various cellular activities is well known. It has been documented that both the notochord and extracellular matrix materials (ECM) induce somite chrondrogenesis. We believe that the ECM modulates the intracellular cAMP level during chondrogenic differentiation. The studies indicated that notochordal induction, which resulted in somite chondrogenesis (reflected by increased sulfated glycosaminoglycan synthesis) reduced the intracellular cAMP level in somites. Addition of forskolin and dibutyryl cAMP resulted in increased intracellular cAMP levels and decreased synthesis of sulfated glycosaminoglycans (decreased chondrogenesis). In the case of dibutyryl cAMP, the inhibition of sulfated glycosaminoglycan synthesis was related to the length of exposure time. Thus, the inverse relationship between cAMP content and enhanced chondrogenesis supports the theory that, in somites, a decrease in the intracellular cAMP level may be necessary to trigger chondrogenic differentiation.

Animals↗
PubMed1983

Alterations of renal cortex and medullary glycosaminoglycans in aging dog kidney.

Age-related changes in renal function have been attributed to alterations in the chemical composition of the kidney tissues. Hence, the glycosaminoglycan composition of the renal cortex and medulla at varying age intervals was investigated. Glycosaminoglycans were isolated from the tissues by means of digestion with collagenase and pronase and purified by ethanol precipitation. Subsequent separation of various polyanions was accomplished by ion exchange chromatography on a Dowex 1-X2 column, using sodium chloride buffers of increasing ionic strengths. The glycosaminoglycans in each fraction were identified and quantitated by digestion with specific enzymes, including hyaluronidase, chondroitinase AC and ABC. The enzyme resistant material was separated and further digested with nitrous acid to quantitate the proportion of heparon sulfate. The results indicate that the glycosaminoglycan content of the renal medulla was much higher than the cortex at all the age intervals studied, and age-induced reduction was mainly cortical. There was a significant reduction in the heparan sulfate content of the cortex in aging. Interestingly, the major glycosaminoglycan content of the medulla was hyaluronic acid, which showed a sharp increase during aging, whereas heparan sulfate declined. Chondroitin sulfate was not altered due to age in either tissue. The molecular weight of hyaluronic acid was determined by column chromatography. Results indicate that the size of hyaluronate in the cortex was small and did not vary with age. In the medulla of the younger age group, a considerable amount of large size hyaluronate was observed. As age increased, the size decreased. The results strongly suggest that alteration in the renal glycosaminoglycans may be partly responsible for the age related protinuria and ionic imbalance.

Aging↗
PubMed1983

Alterations in the rat renal glycosaminoglycans in streptozotocin-induced diabetes.

The effect of streptozotocin-induced diabetes on the glycosaminoglycan composition of rat renal cortical tissue was evaluated. Glycosaminoglycans were isolated and purified from the kidney cortex of control and diabetic rats by means of digestion with collagenase, pronase and ethanol precipitation. Subsequent fractionation was performed by ion exchange chromatography on Dowex 1-X2 Cl using various concentrations of sodium chloride solution. The glycosaminoglycan in each fraction was characterized by digestion with hyaluronidase, chondroitinase AC and ABC. The undigested glycosaminoglycans were separated after each enzyme digestion and quantitated. The glycosaminoglycan composition of each fraction was computed from the enzyme digestion profile. The results indicate that in renal cortex of streptozotocin induced diabetic rats there was a significant reduction in the levels of dermatan sulfate, heparan sulfate and hyaluronic acid, while the chondroitin sulfate remained unaffected. In light of this finding, the significance of these anionic polysaccharides in renal functions is discussed.

Animals↗
PubMed1981

Proteoglycan synthesis by sternal chondrocytes perturbed with vitamin A.

Proteoglycan synthesis by sternal chondrocytes was studied in the presence of excess vitamin A (10 i.u./ml). Proteoglycans synthesized by the treated cells were smaller, and had larger amounts of chondroitinase ABC-resistant materials than control cells. Vitamin A-pretreated cells, when provided with normal feeding medium, failed to revert back to normal morphology and synthetic processes. Chondrocyte cultures prelabelled with [35S]-sulphate, when maintained in the presence of excess of vitamin A, showed: (1) increased release of labelled proteoglycans into the medium, and (2) increased (19%) degradation of the proteoglycans. The proteoglycans synthesized by the vitamin A-treated chondrocytes are also incapable of binding with exogenous large molecular weight hyaluronic acid. Thus, high levels of vitamin A modulate the differentiation of chondrocytes by altering cellular synthetic processes.

Animals↗
PubMed1980

Extracellular matrix synthesis in the chick embryo lateral plate prior to and during limb outgrowth.

Little is known at the present time about the molecular basis and mechanisms of morphogenesis. The present study is an attempt to determine what influence the extracellular matrix has on the initial outgrowth of the limb bud. Stage -12 to -18 chick embryo lateral plates were examined in relation to proline and sulfate incorporation into collagen and proteoglycan. The flank and limbs incorporated the same amount of labeled proline and sulfate before stage 16. At stage 16 the flank began to incorporate more of both isotopes until at stage 18 there was twice as much incorporation into the flank as into the limbs. The flank and limbs contained the same type of collagen during the period examined. The limbs contained both large and small proteoglycans but the flank contained only small proteoglycans. These data suggest that the extracellular matrix in the flank and limb regions may play a role in limb outgrowth and that the limb buds at these stages may be more inclined toward cartilage development.

Age Factors↗
PubMed1979

Monomeric and aggregate proteoglycans in the chondrogenic differentiation of embryonic chick limb buds.

Proteoglycan heterogeneity was studied during the in vivo differentiation of embryonic chick limb cartilage. Recently, it has been shown that during the differentation of limb cartilage the proportion of the aggregated form of proteoglycans increases whereas the unassociated monomeric forms decrease, and this has been related to the synthesis of two link proteins at a specific stage of differentation. In this study it is suggested that the appearance of the aggregate formation is also due to synthesis of a stable hyaluronic acid binding region of the core protein. Thus, it can be concluded that differential gene expression for these proteins takes place as a differentiation phenomenon.

Animals↗
PubMed1978

Proteogylcan heterogeneity in embryonic chick articular and epiphyseal cartilages.

Proteoglycans from two regions of the chick limb rudiment (articular and epiphyseal) were examined for chemical microheterogeneity. These cartilages are composed of at least two series of proteoglycan variants whose glycosaminoglycan side chains display microheterogeneity with respect to the proportions of 4- and 6-linked ester sulfate. Other differences are noted which are consonant with the hypothesis that extracellular matrix components may be structurally adapted to a tissue's developmental fate or function.

Animals↗