1986 — 1988 |
Davis, Barbara J |
R23Activity Code Description: Undocumented code - click on the grant title for more information. |
Neural Regulation of the Endocrine Pancreas @ University of Rochester
Our objective is to provide a better understanding of the mechanisms leading to deterioration of glucose homeostasis in the elderly. We propose to undertake a set of integrated morphological, functional and biochemical studies of the endocrine pancreas and its autonomic innervation in the C57BL/6NNia mouse at 3, 6, 12, 18, 24 and 30 months of age in order to: 1) define age-correlated changes in the structure and function of the pancreatic islets in this animal model, and 2) determine whether age-correlated changes in pancreatic islet structure and function are due to altered autonomic input to the pancreas. The general morphology of the pancreatic islets will be assessed qualitatively using routine light microscopic techniques (aldehyde-fuchsin-trichrome). Pancreatic islet A, B, D and PP cells will be identified using immunocytochemistry. Cholinergic and adrenergic nerve fibers in the pancreas will be identified using acetylcholinesterase and glyoxylic acid-fluorescence histochemistry, respectively. The volume density of islets and the linear density of nerve fibers within the pancreas will be detemrined using stereological techniques (computer-assisted morphometry). Plasms insulin and glucagon responses to fasting, refeeding after a fast, and to glucose loads will be determined using radioimmunoassays. The activities of cholinergic and adrenergic nerves within the pancreas will be determined by measuring, in extracts of pancreatic tissues, the activities the biosynthetic enzymes cholineacetyl-transferase (CAT) and tyrosine hydroxylase (TOH), respectively. Data will be compared between age groups, using analysis of variance followed by Newman-Kuels tests to determine the effect of age on each parameter measured.
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1 |
1988 — 1989 |
Davis, Barbara J |
R29Activity Code Description: Undocumented code - click on the grant title for more information. |
Neural Regulation of the Endocrine Pancreas in Mice @ University of Rochester
pancreatic islet function; autonomic nervous system; morphology; neural information processing; aging; animal old age; glucose metabolism; nicotinic receptors; insulin; glucagon; adrenergic receptor; image processing; immunochemistry; histochemistry /cytochemistry; laboratory mouse; radioimmunoassay; fasting;
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1 |
1990 |
Davis, Barbara J |
R29Activity Code Description: Undocumented code - click on the grant title for more information. |
Neural Regulation of Endocrine Pancreas in Mice @ University of Rochester
pancreatic islet function; autonomic nervous system; morphology; neural information processing; aging; animal old age; glucose metabolism; cholinergic receptors; insulin; glucagon; adrenergic receptor; image processing; immunochemistry; histochemistry /cytochemistry; laboratory mouse; radioimmunoassay; fasting;
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1 |
1992 — 1993 |
Davis, Barbara J |
K11Activity Code Description: Undocumented code - click on the grant title for more information. |
Pathogenesis Studies of Ovarian Toxicants @ North Carolina State University Raleigh
Many environmental, industrial and therapeutic chemicals perturb female reproduction. The ovary is clearly a target for many of these chemicals, but mechanisms of ovarian toxicants are poorly defined. Therefore, this proposal will elucidate mechanisms by which primary ovarian toxicants damage cells essential for reproduction. The ovarian response to chemical insult is evaluated using three specific ovarian toxicants as probes. Cyclophosphamide is used to kill rapidly proliferating cells. Di(2-ethylhexyl) phthalate is used to perturb granulosa cell growth and differentiation. Ethylene glycol monomethyl ether is used to target oocytes. Perturbations in ovarian morphology (quantitative light and electron microscopy studies), and ovarian function (estradiol, progesterone, androstenedione) and pituitary function (FSH, LB) are evaluated with respect to the estrous cycle and time of chemical exposure. The granulosa cell is a central link in the exchange of intraovarian and extraovarian communication; thus, toxic insult to the granulosa cell could result in ovarian dysfunction. Work from this laboratory has determined that the female reproductive toxicant mono(2-ethylhexyl) phthalate decreases FSH mediated cAMP accumulation in cultured rat granulosa cells. Cyclic AMP and estradiol, a cAMP-dependent granulosa cell product and a critical regulatory hormone, will be measured in cultured FSH-stimulated granulosa cells to test the hypothesis that the primary toxicity of mono (2-ethylhexyl) phthalate on granulosa cells is mediated through alterations in FSH-stimulated cAMP accumulation. Structure-activity relationships will then be examined to test the hypothesis that alterations in FSH-stimulated cAMP accumulation is the primary mechanism of female reproductive toxicity of the class of phthalates.
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0.94 |
1994 — 1996 |
Davis, Barbara J |
K11Activity Code Description: Undocumented code - click on the grant title for more information. |
Pathogenesis of Ovarian Toxicants @ North Carolina State University Raleigh
Many environmental, industrial and therapeutic chemicals perturb female reproduction. The ovary is clearly a target for many of these chemicals, but mechanisms of ovarian toxicants are poorly defined. Therefore, this proposal will elucidate mechanisms by which primary ovarian toxicants damage cells essential for reproduction. The ovarian response to chemical insult is evaluated using three specific ovarian toxicants as probes. Cyclophosphamide is used to kill rapidly proliferating cells. Di(2-ethylhexyl) phthalate is used to perturb granulosa cell growth and differentiation. Ethylene glycol monomethyl ether is used to target oocytes. Perturbations in ovarian morphology (quantitative light and electron microscopy studies), and ovarian function (estradiol, progesterone, androstenedione) and pituitary function (FSH, LB) are evaluated with respect to the estrous cycle and time of chemical exposure. The granulosa cell is a central link in the exchange of intraovarian and extraovarian communication; thus, toxic insult to the granulosa cell could result in ovarian dysfunction. Work from this laboratory has determined that the female reproductive toxicant mono(2-ethylhexyl) phthalate decreases FSH mediated cAMP accumulation in cultured rat granulosa cells. Cyclic AMP and estradiol, a cAMP-dependent granulosa cell product and a critical regulatory hormone, will be measured in cultured FSH-stimulated granulosa cells to test the hypothesis that the primary toxicity of mono (2-ethylhexyl) phthalate on granulosa cells is mediated through alterations in FSH-stimulated cAMP accumulation. Structure-activity relationships will then be examined to test the hypothesis that alterations in FSH-stimulated cAMP accumulation is the primary mechanism of female reproductive toxicity of the class of phthalates.
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0.94 |