Connexin 47 mutations increase risk for secondary lymphedema following breast cancer treatment.

Purpose: Secondary lymphedema is a frequent complication of breast cancer associated with surgery, chemotherapy, or radiation following breast cancer treatment. The potential contribution of genetic susceptibility to risk of developing secondary lymphedema following surgical trauma, radiation, and other tissue insults has not been studied.

Experimental Design: To determine whether women with breast cancer and secondary lymphedema had mutations in candidate lymphedema genes, we undertook a case-control study of 188 women diagnosed with breast cancer recruited from the University of Pittsburgh Breast Cancer Program (http://www.

Receptor reserve reflects differential intrinsic efficacy associated with opioid diastereomers.

Structure-activity relationships built around receptor binding or cell-based assays are designed to reveal physiochemical differences between ligands. We hypothesized that agonist receptor reserve may provide a unique approach to distinguish structurally-related agonists exhibiting similar functional characteristics. An intracellular calcium activation assay in Chinese Hamster Ovary (CHO) cells expressing cloned human mu-opioid receptors was developed.

Radioligand binding assays for the glycine site on N-methyl-D-aspartate receptors.

This unit describes a competitive binding assay for the glycine binding site on the NMDA subtype of glutamate receptors in rat brain homogenates. Agonists of the NMDA receptor associated glycine binding site have been proposed as potential therapeutics in cognitive disorders. Conversely, antagonists may be useful in a variety of disorders associated with excessive activation of EAA receptors, including Parkinson, Huntington and Alzheimer Diseases, and neuropathic pain, among others.

Receptor binding profile suggests multiple mechanisms of action are responsible for ibogaine's putative anti-addictive activity.

The indole alkaloid ibogaine (NIH 10567, Endabuse) is currently being examined for its potential utility in the treatment of cocaine and opioid addiction. However, a clearly defined molecular mechanism of action for ibogaine's putative anti-addictive properties has not been delineated. Radioligand binding assays targeting over 50 distinct neurotransmitter receptors, ion channels, and select second messenger systems were employed to establish a broad in vitro pharmacological profile for ibogaine.

Evaluation of the interactions of serotonergic and adrenergic drugs with mu, delta, and kappa opioid binding sites.

Several serotonergic and adrenergic agents were tested for an ability to interact with mu, delta, and kappa opioid binding sites. Spiroxatrine interacted nearly equipotently with all three opioid subtypes, yielding Ki values near 110 nM. A number of other serotonergic and adrenergic agents interacted with affinities in the 1-50 microM range.