Inverse agonism and neutral antagonism at alpha(1a)- and alpha(1b)-adrenergic receptor subtypes.

We have characterized the pharmacological antagonism, i.e., neutral antagonism or inverse agonism, displayed by a number of alpha-blockers at two alpha1-adrenergic receptor (AR) subtypes, alpha(1a)- and alpha(1b)-AR. Constitutively activating mutations were introduced into the alpha(1a)-AR at the position homologous to A293 of the alpha(1b)-AR where activating mutations were previously described. Twenty-four alpha-blockers differing in their chemical structures were initially tested for their effect on the agonist-independent inositol phosphate response mediated by the constitutively active A271E and A293E mutants expressed in COS-7 cells. A selected number of drugs also were tested for their effect on the small, but measurable spontaneous activity of the wild-type alpha(1a)- and alpha(1b)-AR expressed in COS-7 cells. The results of our study demonstrate that a large number of structurally different alpha-blockers display profound negative efficacy at both the alpha(1a)- and alpha(1b)-AR subtypes. For other drugs, the negative efficacy varied at the different constitutively active mutants. The most striking difference concerns a group of N-arylpiperazines, including 8-[2-[4-(5-chloro-2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro [4, 5] decane-7,9-dione (REC 15/3039), REC 15/2739, and REC 15/3011, which are inverse agonists with profound negative efficacy at the wild-type alpha(1b)-AR, but not at the alpha(1a)-AR.

Parvovirus B19 1A complete genome from a fatal case in Brazil

Parvovirus B19 (B19V) infects individuals worldwide and is associated with an ample range of pathologies and clinical manifestations. B19V is classified into three distinct genotypes, all identified in Brazil. Here, we report a complete sequence of a B19V genotype 1A that was obtained by high-throughput metagenomic sequencing. This genome provides information that will contribute to the studies on B19V epidemiology and evolution.

A-1A Supplemental Security Income Program, January 2004

Monthly report from the Iowa Department of Human Services on Supplemental Security Income Program (SSI).

A-1A Supplemental Security Income Program, February 2004

Monthly report from Iowa Department of Human Services on income.

A-1A Supplemental Security Income Program, March 2004

Monthly report from the Iowa Department of Human Services on Supplemental Security Income Program (SSI).

A-1A Supplemental Security Income Program, April 2004

Monthly report from the Iowa Department of Human Services on income.

A-1A Supplemental Security Income Program, May 2004

Monthly report from Iowa Department of Human Services on income.

G-1A Appeal Activity in the Public Assistance Programs, July 2002-June 2003

Yearly report from the Iowa Department of Human Services

A-1A Supplemental Security Income Program, June 2004

Monthly report about supplemental income produced by the Iowa Department of Human Services.

A-1A Supplemental Security Income Program, July 2004

Monthly report about supplemental income produced by the Iowa Department of Human Services.

A-1A Supplemental Security Income Program, August 2004

Monthly report about supplemental income produced by the Iowa Department of Human Services.

A-1A Supplemental Security Income Program, September 2004

Supplemental Security Income Program

A-1A Supplemental Security Income Program, October 2004

Supplemental Security Income Program

A-1A Supplemental Security Income Program, November 2004

Supplemental Security Income Program

A-1A Supplemental Security Income Program, February 2005

Supplemental security income program