Dan Shelly | University of Cincinnati (original) (raw)

Papers by Dan Shelly

Comparative Biochemistry and Physiology Part A: Physiology, 1997

American Journal of Physiology Cell Physiology, Nov 1, 2004

This study uses genetically altered mice to examine the contribution of the Na + -K + -ATPase α 2... more This study uses genetically altered mice to examine the contribution of the Na + -K + -ATPase α 2 catalytic subunit to resting potential, excitability, and contractility of the perinatal diaphragm. The α 2 protein is reduced by 38% in α 2 -heterozygous and absent in α 2 - ...

Gene, Jan 26, 2016

Intraarticular steroid injection has been the mainstay of short-term treatment of knee osteoarthr... more Intraarticular steroid injection has been the mainstay of short-term treatment of knee osteoarthritis (OA) pain. However, the duration of therapeutic effect from a single injection is not as long as desired. In this study we use a viscous formulation of triamcinolone acetate (TCA) in hyaluronic acid to prolong the anti-allodynia effect of that steroid. OA was induced in mice by a partial medial meniscectomy. Over time the animals' developed a mechanical allodynia in the injected leg. Mice were then given a single intraarticular injection of TCA in a short-acting DMSO formulation, or a standard commercial suspension, or the drug formulated in 5% hyaluronic acid for slow-release. Control injections in OA mice were PBS or 5% hyaluronic acid vehicle. Mechanical allodynia was then monitored over the therapeutic period. Organotypic spinal cord slices and DRG culture were performed to assess whether TCA attenuates expressions of pain mediators induced by interleukin 1β. TCA 40μg in a f...

Annals of the rheumatic diseases, Jan 18, 2016

A key clinical paradox in osteoarthritis (OA), a prevalent age-related joint disorder characteris... more A key clinical paradox in osteoarthritis (OA), a prevalent age-related joint disorder characterised by cartilage degeneration and debilitating pain, is that the severity of joint pain does not strictly correlate with radiographic and histological defects in joint tissues. Here, we determined whether protein kinase Cδ (PKCδ), a key mediator of cartilage degeneration, is critical to the mechanism by which OA develops from an asymptomatic joint-degenerative condition to a painful disease. OA was induced in 10-week-old PKCδ null (PKCδ(-/-)) and wild-type mice by destabilisation of the medial meniscus (DMM) followed by comprehensive examination of the histology, molecular pathways and knee-pain-related-behaviours in mice, and comparisons with human biopsies. In the DMM model, the loss of PKCδ expression prevented cartilage degeneration but exacerbated OA-associated hyperalgesia. Cartilage preservation corresponded with reduced levels of inflammatory cytokines and of cartilage-degrading e...

The American journal of physiology, 1999

Epinephrine and amylin stimulate glycogenolysis, glycolysis, and Na(+)-K(+)-ATPase activity in sk... more Epinephrine and amylin stimulate glycogenolysis, glycolysis, and Na(+)-K(+)-ATPase activity in skeletal muscle. However, it is not known whether these hormones stimulate glycolytic ATP production that is specifically coupled to ATP consumption by the Na(+)-K(+) pump. These studies correlated glycolysis with Na(+)-K(+)-ATPase activity in resting rat extensor digitorum longus and soleus muscles incubated at 30 degrees C in well-oxygenated medium. Lactate production rose three- to fourfold, and the intracellular Na(+)-to-K(+) ratio (Na(+)/K(+)) fell with increasing concentrations of epinephrine or amylin. In muscles exposed to epinephrine at high concentrations (5 x 10(-7) and 5 x 10(-6) M), ouabain significantly inhibited glycolysis by approximately 70% in either muscle and inhibited glycogenolysis by approximately 40 and approximately 75% in extensor digitorum longus and soleus, respectively. In the absence of ouabain, but not in its presence, statistically significant inverse correl...

American journal of physiology. Regulatory, integrative and comparative physiology, 2001

The Na-K-ATPase, which maintains the Na(+) and K(+) gradients across the plasma membrane, can pla... more The Na-K-ATPase, which maintains the Na(+) and K(+) gradients across the plasma membrane, can play a major role in modulation of skeletal muscle contractility. Although both alpha(1)- and alpha(2)-isoforms of the Na-K-ATPase are expressed in skeletal muscle, the physiological significance of these isoforms in contractility is not known. Evaluation of the contractile parameters of mouse extensor digitorum longus (EDL) was carried out using gene-targeted mice lacking one copy of either the alpha(1)- or alpha(2)-isoform gene of the Na-K-ATPase. The EDL muscles from heterozygous mice contain approximately one-half of the alpha(1)- or alpha(2)-isoform, respectively, which permits differentiation of the functional roles of these isoforms. EDL from the alpha(1)(+/-) mouse shows lower force compared with wild type, whereas that from the alpha(2)(+/-) mouse shows greater force. The different functional roles of these two isoforms are further demonstrated because inhibition of the alpha(2)-is...

Journal of Biological Chemistry, 2003

AJP: Cell Physiology, 2004

This study uses genetically altered mice to examine the contribution of the Na+-K+-ATPase α2 cata... more This study uses genetically altered mice to examine the contribution of the Na+-K+-ATPase α2 catalytic subunit to resting potential, excitability, and contractility of the perinatal diaphragm. The α2 protein is reduced by 38% in α2-heterozygous and absent in α2-knockout mice, and α1-isoform is upregulated 1.9-fold in α2-knockout. Resting potentials are depolarized by 0.8–4.0 mV in heterozygous and knockout mice. Action potential threshold, overshoot, and duration are normal. Spontaneous firing, a developmental function, is impaired in knockout diaphragm, but this does not compromise its ability to fire evoked action potential trains, the dominant mode of activation near birth. Maximum tetanic force, rate of activation, force-frequency and force-voltage relationships, and onset and magnitude of fatigue are not changed. The major phenotypic consequence of reduced α2 content is that relaxation from contraction is 1.7-fold faster. This finding reveals a distinct cellular role of the α2-...

AJP: Cell Physiology, 2004

The relative expression of α1 - and α2-Na+/K+-ATPase isoforms found in vascular smooth muscle is ... more The relative expression of α1 - and α2-Na+/K+-ATPase isoforms found in vascular smooth muscle is developmentally regulated and under hormonal and neurogenic control. The physiological roles of these isoforms in vascular function are not known. It has been postulated that the α1-isoform serves a “housekeeping” role, whereas the α2-isoform localizes to a subsarcolemmal compartment and modulates contractility. To test this hypothesis, isoform-specific gene-targeted mice in which the mRNA for either the α1- or the α2-Na+/K+-ATPase isoform was ablated were utilized. Both of these knockouts, [Formula: see text] and [Formula: see text], are lethal; the latter dies at birth, which allows this neonatal aorta to be studied. Isometric force in [Formula: see text]-aorta was more sensitive to contractile agonists and less sensitive to the vasodilators forskolin and sodium nitroprusside (SNP) than wild-type (WT) aorta; [Formula: see text]-aortas had intermediate values. In contrast, neonatal [For...

BioResearch open access, 2014

Respiratory syncytial virus (RSV) is the leading cause of hospitalization due to respiratory illn... more Respiratory syncytial virus (RSV) is the leading cause of hospitalization due to respiratory illness among infants and young children of industrialized countries. There is a lack of understanding of the severe disease mechanisms as well as limited treatment options, none of which are fully satisfactory. This is partly due to lack of a relevant animal model of perinatal RSV infection that mimics moderate to severe disease in infants. We and others have shown mild disease in perinatal lambs with either a bovine or a human A2 strain of RSV. The Memphis 37 clinical strain of human RSV has been used to produce mild to moderate upper respiratory disease in healthy adult volunteers. We hypothesized that the Memphis 37 strain of RSV would infect perinatal lambs and produce clinical disease similar to that in human infants. Perinatal (3- to 5-day-old) lambs were inoculated intranasally with 2 mL/nostril of 1×10(5) focus-forming units (FFU)/mL (n=2) or 2.1×10(8) FFU/mL (n=3) of RSV Memphis 37...

Comparative Biochemistry and Physiology Part A: Physiology, 1997

American Journal of Physiology Cell Physiology, Nov 1, 2004

This study uses genetically altered mice to examine the contribution of the Na + -K + -ATPase α 2... more This study uses genetically altered mice to examine the contribution of the Na + -K + -ATPase α 2 catalytic subunit to resting potential, excitability, and contractility of the perinatal diaphragm. The α 2 protein is reduced by 38% in α 2 -heterozygous and absent in α 2 - ...

Gene, Jan 26, 2016

Intraarticular steroid injection has been the mainstay of short-term treatment of knee osteoarthr... more Intraarticular steroid injection has been the mainstay of short-term treatment of knee osteoarthritis (OA) pain. However, the duration of therapeutic effect from a single injection is not as long as desired. In this study we use a viscous formulation of triamcinolone acetate (TCA) in hyaluronic acid to prolong the anti-allodynia effect of that steroid. OA was induced in mice by a partial medial meniscectomy. Over time the animals' developed a mechanical allodynia in the injected leg. Mice were then given a single intraarticular injection of TCA in a short-acting DMSO formulation, or a standard commercial suspension, or the drug formulated in 5% hyaluronic acid for slow-release. Control injections in OA mice were PBS or 5% hyaluronic acid vehicle. Mechanical allodynia was then monitored over the therapeutic period. Organotypic spinal cord slices and DRG culture were performed to assess whether TCA attenuates expressions of pain mediators induced by interleukin 1β. TCA 40μg in a f...

Annals of the rheumatic diseases, Jan 18, 2016

A key clinical paradox in osteoarthritis (OA), a prevalent age-related joint disorder characteris... more A key clinical paradox in osteoarthritis (OA), a prevalent age-related joint disorder characterised by cartilage degeneration and debilitating pain, is that the severity of joint pain does not strictly correlate with radiographic and histological defects in joint tissues. Here, we determined whether protein kinase Cδ (PKCδ), a key mediator of cartilage degeneration, is critical to the mechanism by which OA develops from an asymptomatic joint-degenerative condition to a painful disease. OA was induced in 10-week-old PKCδ null (PKCδ(-/-)) and wild-type mice by destabilisation of the medial meniscus (DMM) followed by comprehensive examination of the histology, molecular pathways and knee-pain-related-behaviours in mice, and comparisons with human biopsies. In the DMM model, the loss of PKCδ expression prevented cartilage degeneration but exacerbated OA-associated hyperalgesia. Cartilage preservation corresponded with reduced levels of inflammatory cytokines and of cartilage-degrading e...

The American journal of physiology, 1999

Epinephrine and amylin stimulate glycogenolysis, glycolysis, and Na(+)-K(+)-ATPase activity in sk... more Epinephrine and amylin stimulate glycogenolysis, glycolysis, and Na(+)-K(+)-ATPase activity in skeletal muscle. However, it is not known whether these hormones stimulate glycolytic ATP production that is specifically coupled to ATP consumption by the Na(+)-K(+) pump. These studies correlated glycolysis with Na(+)-K(+)-ATPase activity in resting rat extensor digitorum longus and soleus muscles incubated at 30 degrees C in well-oxygenated medium. Lactate production rose three- to fourfold, and the intracellular Na(+)-to-K(+) ratio (Na(+)/K(+)) fell with increasing concentrations of epinephrine or amylin. In muscles exposed to epinephrine at high concentrations (5 x 10(-7) and 5 x 10(-6) M), ouabain significantly inhibited glycolysis by approximately 70% in either muscle and inhibited glycogenolysis by approximately 40 and approximately 75% in extensor digitorum longus and soleus, respectively. In the absence of ouabain, but not in its presence, statistically significant inverse correl...

American journal of physiology. Regulatory, integrative and comparative physiology, 2001

The Na-K-ATPase, which maintains the Na(+) and K(+) gradients across the plasma membrane, can pla... more The Na-K-ATPase, which maintains the Na(+) and K(+) gradients across the plasma membrane, can play a major role in modulation of skeletal muscle contractility. Although both alpha(1)- and alpha(2)-isoforms of the Na-K-ATPase are expressed in skeletal muscle, the physiological significance of these isoforms in contractility is not known. Evaluation of the contractile parameters of mouse extensor digitorum longus (EDL) was carried out using gene-targeted mice lacking one copy of either the alpha(1)- or alpha(2)-isoform gene of the Na-K-ATPase. The EDL muscles from heterozygous mice contain approximately one-half of the alpha(1)- or alpha(2)-isoform, respectively, which permits differentiation of the functional roles of these isoforms. EDL from the alpha(1)(+/-) mouse shows lower force compared with wild type, whereas that from the alpha(2)(+/-) mouse shows greater force. The different functional roles of these two isoforms are further demonstrated because inhibition of the alpha(2)-is...

Journal of Biological Chemistry, 2003

AJP: Cell Physiology, 2004

This study uses genetically altered mice to examine the contribution of the Na+-K+-ATPase α2 cata... more This study uses genetically altered mice to examine the contribution of the Na+-K+-ATPase α2 catalytic subunit to resting potential, excitability, and contractility of the perinatal diaphragm. The α2 protein is reduced by 38% in α2-heterozygous and absent in α2-knockout mice, and α1-isoform is upregulated 1.9-fold in α2-knockout. Resting potentials are depolarized by 0.8–4.0 mV in heterozygous and knockout mice. Action potential threshold, overshoot, and duration are normal. Spontaneous firing, a developmental function, is impaired in knockout diaphragm, but this does not compromise its ability to fire evoked action potential trains, the dominant mode of activation near birth. Maximum tetanic force, rate of activation, force-frequency and force-voltage relationships, and onset and magnitude of fatigue are not changed. The major phenotypic consequence of reduced α2 content is that relaxation from contraction is 1.7-fold faster. This finding reveals a distinct cellular role of the α2-...

AJP: Cell Physiology, 2004

The relative expression of α1 - and α2-Na+/K+-ATPase isoforms found in vascular smooth muscle is ... more The relative expression of α1 - and α2-Na+/K+-ATPase isoforms found in vascular smooth muscle is developmentally regulated and under hormonal and neurogenic control. The physiological roles of these isoforms in vascular function are not known. It has been postulated that the α1-isoform serves a “housekeeping” role, whereas the α2-isoform localizes to a subsarcolemmal compartment and modulates contractility. To test this hypothesis, isoform-specific gene-targeted mice in which the mRNA for either the α1- or the α2-Na+/K+-ATPase isoform was ablated were utilized. Both of these knockouts, [Formula: see text] and [Formula: see text], are lethal; the latter dies at birth, which allows this neonatal aorta to be studied. Isometric force in [Formula: see text]-aorta was more sensitive to contractile agonists and less sensitive to the vasodilators forskolin and sodium nitroprusside (SNP) than wild-type (WT) aorta; [Formula: see text]-aortas had intermediate values. In contrast, neonatal [For...

BioResearch open access, 2014

Respiratory syncytial virus (RSV) is the leading cause of hospitalization due to respiratory illn... more Respiratory syncytial virus (RSV) is the leading cause of hospitalization due to respiratory illness among infants and young children of industrialized countries. There is a lack of understanding of the severe disease mechanisms as well as limited treatment options, none of which are fully satisfactory. This is partly due to lack of a relevant animal model of perinatal RSV infection that mimics moderate to severe disease in infants. We and others have shown mild disease in perinatal lambs with either a bovine or a human A2 strain of RSV. The Memphis 37 clinical strain of human RSV has been used to produce mild to moderate upper respiratory disease in healthy adult volunteers. We hypothesized that the Memphis 37 strain of RSV would infect perinatal lambs and produce clinical disease similar to that in human infants. Perinatal (3- to 5-day-old) lambs were inoculated intranasally with 2 mL/nostril of 1×10(5) focus-forming units (FFU)/mL (n=2) or 2.1×10(8) FFU/mL (n=3) of RSV Memphis 37...