John J. Harrington

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The C family G-protein-coupled receptors contain members that sense amino acid and extracellular cations, of which calcium-sensing receptor (CASR) is the prototypic extracellular calcium-sensing receptor. Some cells, such as osteoblasts in bone, retain responsiveness to extracellular calcium in CASR-deficient mice, consistent with the existence of another(More)
BACKGROUND GPRC6A is a widely expressed orphan G-protein coupled receptor that senses extracellular amino acids, osteocalcin and divalent cations in vitro. The physiological functions of GPRC6A are unknown. METHODS/PRINCIPAL FINDINGS In this study, we created and characterized the phenotype of GPRC6A(-/-) mice. We observed complex metabolic abnormalities(More)
Analogues of the natural product noscapine were synthesized and their potential as antitumor agents evaluated. The discovery of a novel regioselective O-demethylation facilitated the synthesis of the potent aniline 6, which arrests mammalian cells in the G2/M phase of the cell cycle at 0.1 microM and also affects tubulin polymerization. Aniline 6 is orally(More)
BACKGROUND The prevalence and nature of sleep disorders in primary care has not been widely studied. As part of a survey conducted in 5 family practice offices in North Carolina, we screened adult patients for sleep syndromes and sought to ascertain which demographic status and health status were associated with these disorders. METHODS We approached 2963(More)
The NF-kappaB pathway plays a critical role in regulating cellular processes such as immune responses, stress responses, apoptosis, proliferation and differentiation, whereas dysfunction of this pathway has been associated with numerous cancer and immune disorders. We have applied our Random Activation of Gene Expression technology to an NF-kappaB reporter(More)
Flap endonuclease-1 (FEN1) is a key enzyme involved in base excision repair (BER), a primary pathway utilized by mammalian cells to repair DNA damage. Sensitization to DNA damaging agents is a potential method for the improvement of the therapeutic window of traditional chemotherapeutics. In this paper, we describe the identification and SAR of a series of(More)
The study compares polysomnography (PSG) and cardiopulmonary coupling (CPC) sleep quality variables in patients with (1) obstructive sleep apnea (OSA) and (2) successful and unsuccessful continuous positive airway pressure (CPAP) response. PSGs from 50 subjects (32 F/18 M; mean age 48.4 ± 12.29 years; BMI 34.28 ± 9.33) were evaluated. OSA patients were(More)
Analogues of the natural product noscapine were synthesized, and their potential as antitumor agents were examined. The discovery of a novel regio- and stereoselective O-demethylation led to the synthesis of several O-alkylated analogues that induced an unexpected S-phase arrest of mammalian cells. Compound 4a was the most potent analogue inhibiting cell(More)
High-throughput target discovery requires robust disease models and the ability to rapidly survey the genome for function. In the post-genomics era, there has been a strong emphasis placed upon "gene-to-function" approaches that take advantage of the large amount of gene sequence information now available. Here, we advocate a return to "function-to-gene"(More)
OBJECTIVE Sleep-related material in medical textbooks may be the only method by which physicians educate themselves about sleep. In the last decade significant progress in sleep research has been made, but how textbooks in relevant fields reflect it has not been examined. Our purpose was to review and compare (2005 with 1998) sleep content in representative(More)