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The development of the enteric nervous system is dependent upon the actions of glial cell line-derived neurotrophic factor (GDNF) on neural crest-derived precursor cells in the embryonic gut. GDNF treatment of cultured enteric precursor cells leads to an increase in the number of neurons that develop and/or survive. Here we demonstrate that, although GDNF(More)
The development of enteric and sympathetic neurons from neural crest precursor cells is regulated by signals produced by the embryonic environments to which the cells migrate. Bone morphogenetic proteins (BMPs) are present in the developing embryo and act to induce neuronal differentiation and noradrenergic properties of neural crest cells. We have(More)
Amines whose pK values lie between about 5 and 9 are lysosomotropic because lysosomes are acidic intracellular compartments. If such amines bear long hydrophobic chains, they become detergents upon protonation inside the lysosomes, rupturing the lysosomal membrane and killing the cell. Six types of lysosomotropic amines have been prepared that all behave in(More)
Nerve growth factor (NGF) acutely modulates synaptic transmission between sympathetic neurons and their cardiac myocyte targets. NGF also has developmental effects in establishing the level of synaptic transmission between sympathetic neurons and myocytes in culture, although little is known about the mechanisms by which NGF influences this synaptic(More)
Cancer cells need cholesterol to make new membrane. They get it either by de novo synthesis or from low-density lipoprotein (LDL), or both. Some types of cancer have very high LDL requirements. LDL particles, which circulate in the blood, contain a cholesteryl ester core surrounded by a phospholipid coat containing apoproteins that are recognized by LDL(More)
In the peripheral nervous system, enteric and sympathetic neurons develop from multipotent neural crest cells. While local environmental signals in the gut and in the region of the sympathetic ganglia play a role in the choice of cell fate, little is known about the mechanisms that underlie restriction to specific neuronal phenotypes. We investigated the(More)
The 3-substituted benzazepinone, L-692,429 (compound 1), is the prototype compound of a novel class of compounds that stimulate release of growth hormone (GH). The molecule evolved from efforts to identify a non-peptide mimic of the growth hormone-releasing hexapeptide, GHRP-6. Compound 1 is prepared by sequential attachment of dimethyl-beta-alanine and(More)
In order to establish whether CyP is the pharmacologically relevant CsA receptor, the CyP binding v immunosuppressive activity was measured for an extensive, structurally varied group of CsA analogues. Overall, CyP binding was found to parallel immunosuppressive activity. Other than MeAla6-CsA, the few exceptions to the correlation could be ascribed to(More)
The continuing discovery and development of beta-lactams as antibiotics has had an unparalleled impact on the overall health and well-being of society. Recently, appropriately substituted cephalosporins were shown to be potent inhibitors of elastase, suggesting a novel therapeutic role for the beta-lactams in the control of emphysema and other degenerative(More)
Bioactive primary and secondary amines, when acylated with the Z-Gly-Phe group, are transported into pinocytic cells, such as macrophages, P-815 mastocytoma, SV-40 3T3, and leukemia 1210, much faster than the parent compounds. Amines such as lysosomotropic detergents [R. A. Firestone, J. M. Pisano, and R. J. Bonney, J. Med. Chem., 22, 1130 (1979) and(More)