Emory University

Daiichi Pharmaceutical Co., Ltd.

R Wayne Alexander

Russell M Medford

Sampath Parthasarathy

Bobby V Khan

Margaret K Offermann

Mark M Goodman

Randolph E Patterson

Ken'ichi Nishida

David Chappell

Murphy T J

David G Harrison

Compounds of the invention have the general structure ##STR1## X, Y or Z are, respectively independently, H, F or an isotope thereof, Br or an isotope thereof, I or an isotope thereof, At or an isotope thereof, (R.sub.1)W or (R.sub.2)V and R is --(R.sub.1)W, when W is H or F or an isotope thereof, R.sub.1 is linear or branched alkyl of 1-4 carbon atoms, R.sub.2 is vinyl, V is I or an isotope thereof and at least one of X, Y or Z is not H. The compounds of the invention bind to PK receptors.

Haloisoquinoline carboxamide

Dithiocarboxylates, and in particular, dithiocarbamates, block the induced expression of the endothelial cell surface adhesion molecule VCAM-1, and are therefor useful in the treatment of cardiovascular disease, including atherosclerosis, post-angioplasty restenosis, coronary artery diseases, and angina, as well as noncardiovascular inflammatory diseases that are mediated by VCAM-1.

Treatment for atherosclerosis and other cardiovascular and inflammatory

A method for the treatment of cardiovascular diseases and noncardiovascular inflammatory diseases that are mediated by VCAM-1 is provided that includes the removal, decrease in the concentration of, or prevention of the formation of oxidized polyunsaturated fatty acids, or interferes with a complex formed between a polyunsaturated fatty acid or an oxidized polyunsaturated fatty acid and a protein or peptide that mediates the expression of VCAM-1. A method is also provided for suppressing the expression of a redox-sensitive gene or activating a gene that is suppressed through a redox-sensitive pathway, that includes administering an effective amount of a substance that prevents the oxidation of the oxidized signal, and typically, the oxidation of a polyunsaturated fatty acid, or interferes with a complex formed between the oxidized signal and a protein or peptide that mediates the expression of the redox gene.

The cloning, nucleotide and deduced amino acid sequences of the gene encoding endothelial nitric oxide synthase are described. The sequence contains binding domains for calcium/calmodulin, FMN, FAD and NADPH. The enzyme has a molecular weight of 133,413 M.sub.r. The amino terminal portion of the enzyme exhibits a proline-rich region and several sites for proline-directed phosphorylation as well as a potential substrate site for acyl transferase. DNA probes prepared from the nucleic acid sequence are useful in research and diagnostically to determine the level of nitric oxide synthase mRNA expressed by endothelial cells both in cell culture and in intact tissues. These probes are also useful for detecting genetic abnormalities. The nitric oxide synthase gene is transfected into blood vessels in vivo for enhanced synthesis of nitric oxide synthase, resulting in increased production of nitric oxide. The gene is also transfected into host cells that do not normally express the enzyme for production of endothelial nitric oxide synthase in large volumes.

Bovine endothelial nitric oxide synthase nucleic acids

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Atlanta, GA, United States of America

R Wayne Alexander