Thomas W. Smith

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By using a potential-dependent J-aggregate-forming delocalized lipophilic cation, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine++ + iodide (JC-1), we find that membrane potentials across mitochondria in a living cell can be heterogeneous. Remarkably, even within a long contiguous mitochondrion, regional heterogeneity in membrane(More)
The spectral properties of a novel membrane potential sensitive probe (JC-1) were characterized in aqueous buffers and in isolated cardiac mitochondria. JC-1 is a carbocyanine with a delocalized positive charge. It formed under favorable conditions a concentration-dependent fluorescent nematic phase consisting of J-aggregates. When excited at 490 nm, the(More)
Frontotemporal dementia (FTD) with inclusion body myopathy and Paget disease of bone (IBMPFD) is a rare, autosomal-dominant disorder caused by mutations in the valosin-containing protein (VCP) gene, a member of the AAA-ATPase gene superfamily. The neuropathology associated with sporadic FTD is heterogeneous and includes tauopathies and frontotemporal lobar(More)
Enkephalin, a natural ligand for opiate receptors is composed of the pentapepides H-Tyr-Gly-Gly-Phe-Met-OH and H-Tyr-Gly-Gly-Phe-Leu-OH. The evidence is based on the determination of the amino acid sequence of natural enkephalin by the dansyl-Edman procedure and by mass spectrometry followed by synthesis and comparison of the natural and synthetic peptides.
Nitric oxide (NO) synthesized from L-arginine is a ubiquitous intracellular chemical messenger and is involved in signal transduction in diverse mammalian cells, including vascular endothelium and neuronal tissues. The role of the NO-signaling pathway in the direct modulation of cardiac function is less well characterized. In this report, the effects of(More)
In Alzheimer's disease (AD), affected neurons accumulate beta amyloid protein, components of which can induce mouse microglia to express the high-output isoform of nitric oxide synthase (NOS2) in vitro. Products of NOS2 can be neurotoxic. In mice, NOS2 is normally suppressed by transforming growth factor beta 1 (TGF-beta 1). Expression of TGF-beta 1 is(More)
Mdm2 is required to negatively regulate p53 activity at the peri-implantation stage of early mouse development. However, the absolute requirement for Mdm2 throughout embryogenesis and in organogenesis is unknown. To explore Mdm2-p53 signaling in osteogenesis, Mdm2-conditional mice were bred with Col3.6-Cre-transgenic mice that express Cre recombinase in(More)
Nitric oxide synthase (NOS) isoforms are discovered in an increasing variety of cell types with different roles in signaling. The inducible NOS (i.e. iNOS or NOS II) is expressed in cardiac myocytes in response to specific cytokines. Independent of iNOS induction, however, receptor-dependent signaling is modulated by a constitutive nitric oxide (NO)(More)
In isolated adult rat myocytes, we tested the hypothesis that metabolic inhibition and simulated ischemia regulate the NADH/NAD+ redox couple with concomitant impairment of energy-dependent process, including contraction and maintenance of high-energy phosphate stores. We developed a method to examine the relationship among the redox couple, ATP content,(More)
Endothelin, a 21-amino acid vasoactive peptide, is among the most potent positively inotropic agents yet described in mammalian heart. Having demonstrated that endothelin's inotropic effect is due, in part, to an apparent sensitization of cardiac myofilaments to intracellular calcium, we determined whether this could be due to a rise in intracellular pH(More)