Daniel T. O'Connor

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From the Department of Medicine (L.T., K.L.H., D.T.O.) and the Center for Molecular Genetics (D.T.O.), University of California at San Diego, La Jolla; and the Veterans Affairs San Diego Healthcare System, San Diego, Calif. (L.T., K.L.H., D.T.O.). Address reprint requests to Dr. O’Connor at the Department of Medicine (9111H), University of California at San(More)
The secretory prohormone chromogranin A (CHGA) is overexpressed in essential hypertension, a complex trait with genetic predisposition, while its catecholamine release-inhibitory fragment catestatin is diminished, and low catestatin predicts augmented adrenergic pressor responses. These findings from studies on humans suggest a mechanism whereby diminished(More)
Catecholamine secretory vesicle core proteins (chromogranins) contain an activity that inhibits catecholamine release, but the identity of the responsible peptide has been elusive. Size-fractionated chromogranins antagonized nicotinic cholinergic-stimulated catecholamine secretion; the inhibitor was enriched in processed chromogranin fragments, and was(More)
OBJECTIVE To investigate the prevalence of and twin pair concordance for endometriosis. DESIGN A questionnaire survey incorporating validation. SETTING An Australia-wide volunteer sample of female monozygotic (MZ) and dizygotic (DZ) twin pairs from the Australian National Health and Medical Research Council Twin Register. PATIENT(S) Twins were(More)
The pore-forming alpha-subunit, Kv1.5, forms functional voltage-gated K(+) (Kv) channels in human pulmonary artery smooth muscle cells (PASMC) and plays an important role in regulating membrane potential, vascular tone, and PASMC proliferation and apoptosis. Inhibited Kv channel expression and function have been implicated in PASMC from patients with(More)
BACKGROUND Oxygen free radicals may play roles in hypertension both in arteriolar constriction and in formation of lesions. OBJECTIVE To quantify free radical production in blood plasma of genetic hypertensives. DESIGN Hydrogen peroxide levels were measured, because it is one of the most stable reactive oxygen species. METHODS An electrode technique(More)
RATIONALE Dopamine beta-hydroxylase (DBH) plays an essential role in catecholamine synthesis by converting dopamine into norepinephrine. Here we systematically investigated DBH polymorphisms associated with enzymatic activity as well as autonomic and blood pressure (BP)/disease phenotypes in vivo. METHODS AND RESULTS Seventy genetic variants were(More)
BACKGROUND Chromogranin A, coreleased with catecholamines by exocytosis, is cleaved to the catecholamine release-inhibitory fragment catestatin. We identified a natural nonsynonymous variant of catestatin, Gly364Ser, that alters human autonomic function and blood pressure. METHODS AND RESULTS Gly364Ser heterozygotes and controls underwent physiological(More)
Tissue-type plasminogen activator (t-PA) is a serine protease that plays a central role in the regulation of intravascular thrombolysis. The acute release of t-PA in vivo is induced by a variety of stimuli including exercise, trauma, and neural stimulation. These types of stimuli also result in sympathoadrenal activation and exocytotic release of amines and(More)
The novel chromogranin A fragment catestatin (bovine chromogranin A(344-364); RSMRLSFRARGYGFRGPGLQL) is a potent inhibitor of catecholamine release (IC50, approximately 0.2-0.3 microM) by acting as a nicotinic cholinergic antagonist. To define the minimal active region within catestatin, we tested the potencies of synthetic serial three-residue deletion(More)