322 research outputs found

    God Calls to Business

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    The Social significance of public housing, with special emphasis on the north side project

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    Social significance is the quality of being important to the welfare of human society or the meaning of any institution to members of society. The purpose of this study is to find out how Public Housing has affected the welfare of the citizens of Omaha generally, and how the Logan Fontenelle Homes Project has affected the social conditions of those people who formerly lived in that area as well as those who now live in the project

    A Putative M 3 Muscarinic Cholinergic Receptor of High Molecular Weight Couples to Phosphoinositide Hydrolysis in Human SK-N-SH Neuroblastoma Cells

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    The M 1 -selective (high affinity for pirenzepine) muscarinic acetylcholine receptor (mAChR) antagonist pirenzepine displaced both N -[ 3 H]methylscopolamine ([ 3 H]NMS) and [ 3 H]qui-nuclidinylbenzilate from intact human SK-N-SH neuroblastoma cells with a low affinity ( K i = 869–1,066 nM), a result indicating the predominance of the M 2 or M 3 (low affinity for pirenzepine) receptor subtype in these cells. Whereas a selective M 2 agent, AF-DX 116 {11–2[[2-[(diethylamino)methyl]-1-piperidinyl]-acetyl]-5,11-dihydro-6 H -pyrido[2,3- b ][1,4]benzodiazepin-6-one} bound to the mAChRs with a very low affinity ( K i = 6.0 Μ M ), 4-diphenylacetoxy- N -methylpiperidine methiodide (4-DAMP), an agent that binds with high affinity to the M 3 subtype, potently inhibited [ 3 H]NMS binding ( K i = 7.2 n M ). 4-DAMP was also 1,000-fold more effective than AF-DX 1 16 at blocking stimulated phosphoinositide (PPI) hydrolysis in these cells. Covalent labeling studies (with [ 3 H]propylbenzilylcholine mustard) suggest that the size of the SK-N-SH mAChR (M r = 81.000–98,000) distinguishes it from the predominant mAChR species in rat cerebral cortex (M r =66,000), an M 1 -enriched tissue. These results provide the first demonstration of a neural M 3 mAChR subtype that couples to PPI turnover.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65720/1/j.1471-4159.1988.tb03008.x.pd

    Developmental and Regional Studies of the Metabolism of Inositol 1,4,5-Trisphosphate in Rat Brain

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    Coupling of CNS receptors to phosphoinositide turnover has previously been found to vary with both age and brain region. To determine whether the metabolism of the second messenger inositol 1,4,5-trisphosphate also displays such variations, activities of inositol 1,4,5-trisphosphate 5′-phosphatase and 3′-kinase were measured in developing rat cerebral cortex and adult rat brain regions. The 5′-phosphatase activity was relatively high at birth (∼50% of adult values) and increased to adult levels by 2 weeks postnatal. In contrast, the 3′-kinase activity was low at birth and reached ∼50% of adult levels by 2 weeks postnatal. In the adult rat, activities of the 3′-kinase were comparable in the cerebral cortex, hippocampus, and cerebellum, whereas much lower activities were found in hypothalamus and pons/medulla. The 5′-phosphatase activities were similar in cerebral cortex, hippocampus, hypothalamus, and pons/medulla, whereas 5-to 10-fold higher activity was present in the cerebellum. The cerebellum is estimated to contain 50–60% of the total inositol 1,4,5-trisphosphate 5′-phosphatase activity present in whole adult rat brain. The localization of the enriched 5′-phosphatase activity within the cerebellum was examined. Application of a histochemical lead-trapping technique for phosphatase indicated a concentration of inositol 1,4,5-trisphosphate 5′-phosphatase activity in the cerebellar molecular layer. Further support for this conclusion was obtained from studies of Purkinje cell-deficient mutant mice, in which a marked decrement of cerebellar 5′-phosphatase was observed. These results suggest that the metabolic fate of inositol 1,4,5-trisphosphate depends on both brain region and stage of development.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65545/1/j.1471-4159.1990.tb01976.x.pd

    Inositol Lipids and Signal Transduction in the Nervous System: An Update

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    The role that inositol lipids play in cellular signaling events in eukaryotic cells remains one of the most intensively investigated areas of cell biology. In this respect, phosphoinositide-mediated signal transduction in the CNS is no exception; major advances have been made since a previous review on this subject (Fisher and Agranoff, 1987). Not only have stimulated phosphoinositide turnover and its physiological sequelae been demonstrated repeatedly in a variety of neural preparations, but, in addition, the detailed molecular mechanisms underlying these events continue to unfold. Here we review the progress that has occurred in selected aspects of this topic since 1987. In the first two sections of this article, emphasis is placed on novel functional roles for the inositol lipids and on recent insights into the molecular characteristics and regulation of three key components of the phosphoinositide signal transduction system, namely, the inositol lipid kinases, phospholipases C (PLCs), and the inositol 1,4,5-trisphosphate[I(1,4,5)P 3 ] receptor. The metabolic fate of I(1,4,5)P 3 in neural tissues, as well as its control, is also detailed. Later we focus on identification of the multiple receptor subtypes that are coupled to inositol lipid turnover and discuss possible strategies for intervention into phosphoinositide-mediated signal transduction. Due to space limitations, an extensive evaluation of the diacylglycerol/protein kinase C (DAG/PKC) limb of the signal transduction pathway is not included (for reviews, see Nishizuka, 1988; Kanoh et al., 1990).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65626/1/j.1471-4159.1992.tb09273.x.pd

    Enhanced Coupling of Neonatal Muscarinic Receptors in Rat Brain to Phosphoinositide Turnover

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    The relationship between the density of the muscarinic receptor in developing rat cerebral cortex and its coupling to phosphoinositide turnover is examined. Tissue slices from rats of various ages were incubated with myo- [2- 3 H]inositol, and the effect of carbamoylcholine on the release of total inositol phosphates was determined. Binding of [ 3 H]quinuclidinyl benzilate was determined in the same tissue. Although muscarinic receptor density in day-18 embryonic cortex was only 5% of that in the adult, the maximal response of stimulated phosphoinositide turnover to carbamoylcholine (1–10 m M ) was at the adult level (i.e., threefold increase). Comparison of the dependence of the turnover on carbamoylcholine concentration revealed that in neonates, the dose-response curve was shifted to the left, giving a half-maximal effect at concentrations approximately tenfold lower than that in the adult. In addition, the partial muscarinic agonists oxotremorine-2 and bethanechol were both more efficacious in young rats than in adults. The differences could not be accounted for either by alterations in agonist affinity for the receptor or by the presence of “spare” muscarinic receptors. These results indicate that muscarinic receptors in fetal and newborn rat cerebral cortex are more efficiently coupled to stimulation of phosphoinositide turnover than in the adult.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66062/1/j.1471-4159.1987.tb05754.x.pd
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