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Biomedical subjects

S K Ahuja

Publications and source records attributed to S K Ahuja.

8 recordsLinked to original sources

Molecular evolution of the human interleukin-8 receptor gene cluster.

Interleukin-8 (IL-8) is the prototype for a family of at least eight neutrophil chemoattractants whose genes map to human chromosome 4q13-q21. Two human IL-8 receptors, IL8RA and IL8RB, are known from cDNA cloning; IL8RA is a promiscuous receptor for at least two other related ligands, GRO alpha and NAP-2. We now report cloning of the genes for IL8RA, IL8RB and a recently inactivated pseudogene of receptor A (IL8RAP). These form a cluster of only three genes in the superfamily of G protein-coupled receptors (GPCRs) and map to 2q34-q35. The coevolutionary diversity displayed by the IL-8 ligand-receptor complex--ligand promiscuity for IL-8, receptor promiscuity for IL8RA, gene duplication for both ligands and receptors and gene extinction in the case of IL8RAP--is unprecedented for the GPCR superfamily.

Amino Acid Sequence

Age-related qualitative and quantitative changes in the endocrine pancreas of the LA/N-corpulent rat.

Islets of Langerhans in sections from the tail of the pancreas of corpulent LA/N-cp rats and lean controls aged 1, 3, 6 and 9 mo were examined by immunocytochemistry and morphometrically using an automatic image analyzer. The corpulent rats had significantly greater islet volumes at all ages, although islet hypertrophy tended to plateau after 6 mo. By 12 mo age the architecture of the islets was disrupted with large islets fused and showing areas of fibrosis and deposits of hemosiderin. The volume density (v/v, %) of islets in the parenchyma was significantly increased at each age step in corpulent rats reaching over 20% at 9 mo, and was greater in corpulent than in lean rats at all ages. In the corpulent rats, B-cell volume density dramatically with age and at all ages was significantly greater in corpulent than in lean rats. A-cell volume density was significantly greater in the corpulent rats than in lean rats at 1 and 9 mo. The mean B:A cell ratio was greater in corpulent than in lean rats at 3, 6 and 9 mo. There were more D cells per islet in corpulent than in lean rats up to 9 mo. These changes in cell populations were paralleled by qualitative changes in islet morphology and cellular topography such as increasingly irregular islet shape in corpulent animals and by variations in plasma levels of insulin and glucagon. In this strain of rats, obesity is associated with major changes in pancreatic morphology and this correlates strongly with the susceptibility of the strain to atherosclerosis.

Aging

Insulin resistance and impaired glucose tolerance in the atherosclerosis-prone LA/N corpulent rat.

The LA/N-cp rat is, when homozygous for the cp gene, hyperphagous, hyperlipidemic, and corpulent. The corpulent males develop atherosclerotic disease and myocardial lesions while corpulent females and lean rats do not. The fasting plasma glucose concentrations of corpulent rats are in the normal range, but insulin concentrations are mildly elevated in corpulent females and markedly elevated in corpulent males. Glucose tolerance testing reveals a glucose intolerance in corpulent rats in the presence of very high insulin concentrations, and this deficiency is more severe in the male rats. Glucagon concentrations are higher in corpulent rats than lean rats at 3 months of age and decrease progressively with age. In contrast, glucagon concentrations increase with age in lean rats and are higher than those in corpulent rats at 9 months. The islets of Langerhans of corpulent rats exhibit marked hyperplasia that increases with age. The hyperplasia is less extreme in corpulent female rats. The abnormalities suggest that this strain of rats has an insulin resistance leading to impaired glucose tolerance and progressive pancreatic disturbance. This process may be related to an accompanying defect causing elevated concentrations of very low density lipoproteins and correlates with the development of atherosclerotic disease.

Animals