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Restoration of beta-adrenergic signaling in failing cardiac ventricular myocytes via adenoviral-mediated gene transfer.

Akhter, SA; Glower, Donald D Jr; Koch, Walter J; Kypson, Alan P; Lefkowitz, Robert J; McDonald, Patricia H; Peppel, Karsten C; ... (8 authors) (Proc Natl Acad Sci U S A, 1997-10-28)

Cardiovascular gene therapy is a novel approach to the treatment of diseases such as congestive heart failure (CHF). Gene transfer to the heart would allow for the replacement of defective or missing cellular proteins that ...

3-[211At]astato-4-fluorobenzylguanidine: a potential therapeutic agent with prolonged retention by neuroblastoma cells.

Larsen, RH; Vaidyanathan, Ganesan; Zalutsky, Michael Rod; Zhao, XG (Br J Cancer, 1997)

An analogue of meta-iodobenzylguanidine (MIBG) in which an aromatic hydrogen was replaced with fluorine has been found to possess many properties similar to those of the parent compound. Moreover, 4-fluoro-3-iodobenzylguanidine ...

Costimulation of adenylyl cyclase and phospholipase C by a mutant alpha 1B-adrenergic receptor transgene promotes malignant transformation of thyroid follicular cells.

Cottecchia, S; Denef, JF; Dumont, J; Ledent, C; Lefkowitz, Robert J; Parmentier, M; Vassart, G (Endocrinology, 1997-01)

Proliferation of thyroid follicular cells is controlled by three intra-cellular cascades [cAMP, inositol 1,4,5-triphosphate (IP3)/Ca2+/diacylglycerol (DAG), and tyrosine kinases] that are activated by distinct extracellular ...

Receptor and G betagamma isoform-specific interactions with G protein-coupled receptor kinases.

Daaka, Y; Lefkowitz, Robert J; Pitcher, JA; Richardson, M; Robishaw, JD; Stoffel, RH (Proc Natl Acad Sci U S A, 1997-03-18)

The G protein-coupled receptor (GPCR) kinases (GRKs) phosphorylate and desensitize agonist-occupied GPCRs. GRK2-mediated receptor phosphorylation is preceded by the agonist-dependent membrane association of this enzyme. ...

Potentiation of beta-adrenergic signaling by adenoviral-mediated gene transfer in adult rabbit ventricular myocytes.

Drazner, Mark H; Dyer, S; Grant, AO; Koch, Walter J; Lefkowitz, Robert J; Peppel, Karsten C (J Clin Invest, 1997-01-15)

Our laboratory has been testing the hypothesis that genetic modulation of the beta-adrenergic signaling cascade can enhance cardiac function. We have previously shown that transgenic mice with cardiac overexpression of either ...

Ligand-induced overexpression of a constitutively active beta2-adrenergic receptor: pharmacological creation of a phenotype in transgenic mice.

Bond, RA; Lefkowitz, Robert J; Milano, Carmelo Alessio; Rockman, Howard A; Samama, P (Proc Natl Acad Sci U S A, 1997-01-07)

Transgenic overexpression (40- to 100-fold) of the wild-type human beta2-adrenergic receptor in the hearts of mice leads to a marked increase in cardiac contractility, which is apparently due to the low level of spontaneous ...